KR20180030663A - Peptide inhibitors of interleukin-23 receptor and uses thereof for the treatment of inflammatory diseases - Google Patents

Abstract

The present invention provides novel peptide inhibitors of interleukin-23 receptor, and related compositions and methods of using such peptide inhibitors to treat or prevent various diseases and disorders, including inflammatory bowel disease.

Description

Peptide inhibitors of interleukin-23 receptor and uses thereof for the treatment of inflammatory diseases

Cross-reference to related application

This application claims priority to and is a continuation-in-part of U.S. Serial No. 14 / 800,627, filed July 15, 2015, and is a continuation-in-part of International Patent Application No. PCT / US2015 / 040658 filed July 15, , U.S. Provisional Application No. 62 / 264,820, filed December 8, 2015, and U.S. Provisional Application No. 62 / 281,123, filed January 20, 2016, all of which are incorporated herein by reference in their entirety Incorporated herein by reference.

Sequence List

The present application includes a sequence listing submitted electronically in ASCII format, which is incorporated herein by reference in its entirety. The name of the ASCII copy that was made on July 15, 2016 is PRTH-002-03WO_SL.txt, the size of which is 504 KB.

The technical field of the present invention

The present invention relates to novel peptide inhibitors of the interleukin-23 receptor and to its use for the treatment or prevention of a variety of diseases and disorders, including inflammatory bowel disease, Crohn's disease and psoriasis.

Interleukin-23 (IL-23) cytokines have been implicated in the pathogenesis of autoimmune inflammation and related diseases and disorders such as multiple sclerosis, asthma, rheumatoid arthritis, psoriasis, and inflammatory bowel disease (IBD), such as ulcerative colitis and Crohn's disease Has been implicated in playing an important role in. Studies in mouse models of acute and chronic IBD have revealed the primary role of IL-23R and downstream effector cytokines in disease pathogenesis. IL-23R is expressed on various adaptive and innate immune cells, including Th17 cells, γδ T cells, natural killer (NK) cells, dendritic cells, macrophages, and congenital lymphoid cells, which are found abundantly in the intestine. Gene expression and protein levels of IL-23R on the intestinal surface are found to be elevated in IBD patients. It is believed that IL-23 mediates this effect by promoting the development of a population of pathogenic CD4 ⁺ T cells producing IL-6, IL-17, and tumor necrosis factor (TNF).

IL-23 production is abundant in the intestine, where IL-23 acts on T-helper 1 (Th1) and Th17-related cytokines to induce T-cell- and T-cell- Is thought to play an important role in regulating the balance between immune tolerance and immunity, as well as in inhibiting regulatory T cell responses in the digestive tract and in favor of inflammation. In addition, polymorphisms at the IL-23 receptor (IL-23R) are associated with susceptibility to IBD, further establishing an important role for the IL-23 pathway in long-term homeostasis.

 Psoriasis, a chronic skin disease that affects about 2% to 3% of the general population, has been shown to be mediated by a mechanism of T cell inflammation in the body. IL-23 is known to be involved in an important role in the pathogenesis of psoriasis by maintaining chronic autoimmune inflammation through the introduction of interleukin-17, the regulation of T memory cells, and the activation of macrophages Lt; / RTI > interleukins. Expression of IL-23 and IL-23R was found to be increased in tissues of psoriatic patients, and antibodies neutralizing IL-23 showed IL-23-dependent inhibition of psoriasis in an animal model of psoriasis.

IL-23 is a heterodimer composed of the p40 subunit of IL-12, which is a cytokine involved in the generation of interferon-gamma (IFN-y) -generating T helper 1 (T _H 1) cells, and the unique p19 subunit . Although IL-23 and IL-12, both contain p40 subunits, they have different phenotypic characteristics. For example, IL-12 deficient animals are susceptible to inflammatory autoimmune diseases, whereas IL-23 deficient animals are assumed to be IL-6, IL-17, and TNF in the CNS of IL-23 deficient animals ^{+ &} Lt ^{; / RTI} & gt ^; T cells. IL-23 binds to IL-23R, a heterodimeric receptor composed of IL-12R [beta] l and IL-23R subunits. The binding of IL-23 to IL-23R is a result of the Jak-stat signaling molecule, the IL-23 signaling molecule, and the IL-23R signaling molecule, although stat4 activation is substantially weaker in response to IL- Jak2, Tyk2, and Stat1, Stat3, Stat4, and Stat5. IL-23R is structurally associated with Jak2 and associates with Stat3 in a ligand-dependent manner. Unlike IL-12, which primarily acts on naive CD4 (+) T cells, IL-23 primarily acts on memory CD4 (+) T cells.

Efforts have been made to identify therapeutic moieties that inhibit the IL-23 pathway for use in treating IL-23 related diseases and disorders. A number of antibodies have been identified that bind to IL-23 or IL-23R, including ustekinumab, a humanized antibody that binds to IL-23 and has been approved for the treatment of psoriasis. More recently, polypeptide inhibitors have been identified that bind to IL-23R and inhibit the binding of IL-23 to IL-23R (e.g., U.S. Patent Application Publication No. US2013 / 0029907). (Targeting the common p40 subunit) Ustekinumab and ustekinumab, and tildrakizumab (targeting the unique p19 subunit of IL-23), guselkumab, MEDI 2070, and Clinical trials in Crohn's disease or psoriasis using BI-655066 highlight the potential for IL-23 signaling blockade in the treatment of human inflammatory diseases. Such a discovery is promising, but it is a stable, selective, and potent treatment that targets primarily the IL-23 pathway in the intestine, which can be used for the treatment of intestinal inflammation such as intestinal bowel disease, including Crohn's disease, ulcerative colitis, Challenges remain with regard to identifying adult agonists.

It is clear that there is still a need in the art for a novel therapeutic agent targeting the IL-23 pathway that can be used to treat and prevent IL-23-related diseases, including diseases associated with autoimmune inflammation in the intestine. In addition, compounds and methods for specifically targeting IL-23R from the luminal side of the digestive tract may provide therapeutic benefit to IBD patients with local inflammation of intestinal tissue. The present invention addresses the above requirements by binding to IL-23R to inhibit IL-23 binding and signal transduction and providing novel peptide inhibitors suitable for oral administration.

The present invention particularly provides novel peptide inhibitors of IL-23R, and related methods of use.

In a first aspect, the present invention provides a polypeptide comprising an amino acid sequence of the following sequence formula (Xa)

Is cyclized through a bond between X < 4 > and X < 9 &

Or a pharmaceutically acceptable salt or solvate thereof, which inhibits the binding of interleukin-23 (IL-23) to the IL-23 receptor.

X1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12-X13-X14-

In this formula,

X1, X2 and X3 are any amino acid, or are absent,

X4 is any amino acid or chemical moiety capable of forming a bond with X9;

X5, X6, X7 and X8 are any amino acid;

X9 is any amino acid or chemical moiety capable of forming a bond with X4;

X10, X11, X12, X13, X14 and X15 are any amino acid;

X16, X17, X18, X19 and X20 are any amino acid, or are absent.

In certain embodiments of Xa:

X1 is absent; X2 is absent; X3 is absent; X4 is Cys, Abu or Pen; X5 is Ala,? -MeOrn,? -MeSer, Cit, Dap, Dab, Dap (Ac), Gly, Lys, Asn, N-MeGln, N-MeArg, Orn, Gln, Arg, Ser or Thr; X6 is Asp or Thr; X7 is Trp or 6-chloro-Trp; X8 is Glu, Gln or Val; X9 is Cys, Abu or Pen; X10 is 2-Nal, Phe analog, Tyr, or Tyr analog; X11 is 1-Nal, 2-Nal, Phe (3,4- dimethoxy), _{5-hydroxy-Trp, Phe (3,4-Cl 2} ), Trp or Tyr (3-tBu), and; X12 is selected from the group consisting of 3-Pal, Acpc, Acbc, Acvc, Achc, Agp, Aib,? -Diethyl Gly,? -MeLys,? -MeLys , Cav, Cha, Cit, Cpa, D-Asn, Glu, His, hLeu, hArg, Lys, Leu, Octgly, Orn, 4-amino-4-carboxy-piperidine, Arg, Ser, Thr or THP; X13 is selected from the group consisting of Cit, Asp, Dab, Dap, Phe, His, Dap (Peg2-Ac), Dap (pyroglutaric acid), Glu, Homo Arg, Lys, Lys Lys (succinic acid), Asn, Orn, Gln, Arg, Thr, or Val as Lys (IVA), Lys (Peg4-isoGlu-Palm), Lys X14 is Asp, Dab (Ac), Dap (Ac), Phe, His, Lys (Ac), Met, Asn (isobutyl), Gln, Arg, Tyr or Asp (1,4-diaminobutane); X15 is Ala,? Ala, Glu, Gly, Asn, Gln, Arg or Ser.

In certain embodiments of Xa Xa: X1 is absent; X2 is absent; X3 is absent; X4 is Cys, Abu or Pen; X5 is Ala,? -MeOrn,? -MeSer, Cit, Dap, Dab, Dap (Ac), Gly, Lys, Asn, Orn, Gln, Arg, Ser or Thr; X6 is Asp or Thr; X7 is Trp or 6-chloro-Trp; X8 is Gln or Val; X9 is Cys, Abu or Pen; X10 is 2-Nal, Phe analog, Tyr, or Tyr analog; X11 is 1-Nal, 2-Nal, Phe (3,4- dimethoxy), _{5-hydroxy-Trp, Phe (3,4-Cl 2} ), Trp or Tyr (3-tBu), and; X12 is selected from the group consisting of 3-Pal, Acpc, Acbc, Acvc, Achc, Agp, Aib,? -Diethyl Gly,? -MeLys,? -MeLys , Cav, Cha, Cit, Cpa, D-Asn, His, hLeu, hArg, Lys, Leu, Octgly, Orn, 4-amino-4-carboxy-piperidine, or THP; X13 is selected from the group consisting of Cit, Asp, Dab, Dap, Phe, His, Dap (Peg2-Ac), Dap (pyroglutaric acid), Glu, hArg, Lys, Lys ), Lys (IVA), Lys (Peg4-isoGlu-Palm), Lys (pyroglutaric acid), Lys- (succinic acid), Asn, Orn, Gln, Arg, Thr or Val; X14 is Dab (Ac), Dap (Ac), Phe, His, Lys (Ac), Met, Asn, Gln, Arg, or Tyr; X15 is Ala, beta Ala, Gly, Asn, Gln, or Ser.

In certain embodiments of Xa: X1 is absent; X2 is absent; X3 is absent; X4 is Cys, Abu or Pen; X5 is Dap, Dap (Ac), Gly, Lys, Gln, Arg, Ser, Thr or Asn; X6 is Thr; X7 is Trp or 6-chloro-Trp; X8 is Gln; X9 is Cys, Abu or Pen; X10 is 2-Nal, Phe analog, Tyr, or Tyr analog; X11 is 1-Nal, 2-Nal, Phe (3,4- _{dimethoxy), Phe (3,4-Cl 2} ), or Trp; X12 is at least one selected from the group consisting of Acpc, Acbc, Acvc, Achc, Aib, alpha -Diethyl Gly, alpha-MeLys, alpha-MeLys (Ac), alpha-MeLeu, alpha-MeOrn, alpha-MeSer, , Lys, Leu, Arg or THP; Lys (Ac), Lys (benzoic acid), Lys (glutaric acid), Lys (IVA), Lys , Lys (Peg4-isoGlu-Palm), Lys (pyroglutaric acid), Lys- (succinic acid), Asn, Orn, Gln, Arg, or Val; X14 is Dab (Ac), Dap (Ac), His, Lys (Ac), Asn, Gln, or Tyr; X15 is Ala, beta Ala, Gly, Asn, Gln, or Ser.

In certain embodiments of Xa: X1 is absent; X2 is absent; X3 is absent; X4 is Cys, Abu or Pen; X5 is Dap, Dap (Ac), Gln, Ser, Thr or Asn; X6 is Thr; X7 is Trp; X8 is Gln; X9 is Cys, Abu or Pen; X10 is a Phe analog, Tyr, or Tyr analog; X11 is 2-Nal or Trp; X12 is selected from the group consisting of Acpc, Acbc, Acvc, Achc, Aib,? -Diethyl Gly,? -MeLys,? -MeLys (Ac),? -MeLeu,? -MeOrn,? -MeSer,? -MeVal, hLeu, THP; X13 is Cit, Asp, Glu, Lys, Lys (Ac), Asn, or Gln; X14 is Dab (Ac), Asn, or His; X15 is Ala, beta Ala, Gly, Asn, or Gln.

Xa is selected from the group consisting of Cys, Pen, hCys, D-Pen, D-Cys, D-hCys, Met, Glu, Asp, Lys, Orn, Dap, Dab, D-Dap, D-Dab, D 3-chloropropionic acid, 4-chlorobutyric acid, 3-chloroisobutyric acid, 3-chlorobutyric acid, 3-chlorobutyric acid, , Abu,? -Azido-Ala-OH, propargylglycine, 2- (3'-butenyl) glycine, 2-allyl glycine, 2- (3'-butenyl) glycine, 2- Decanyl) glycine, 2- (5'-hexenyl) glycine, or Abu; X7 is Trp, Glu, Gly, Ile, Asn, Pro, Arg, Thr or OctGly, or the corresponding? -Methylamino form of any of the foregoing; D-Dab, D-Dab, D-Asp, D-Glu, D-Lys, Asp, Leu, Val, Phe or Ser, Sec, Abu,? -Azido-Ala-OH, propargylglycine, 2-2-allylglycine, 2- (3'- '- pentenyl) glycine, Ala, hCys, Abu, Met, MeCys, (D) Tyr or 2- (5'- hexenyl) glycine; X10 is Tyr, Phe (4-OMe), 1-Nal, 2-Nal, Aic,? -MePhe, Bip, (D) Cys, Cha, DMT, (D) Tyr, Glu, His, -dimethoxy), hTyr, N-Me- Tyr, Trp, Phe (4-CONH 2), Phe (4- phenoxy), Thr, Tic, Tyr ( 3-tBu), Phe (4-tBu), Phe (4-CN), Phe ( 4-Br), Phe (4-NH 2), Phe (4-F), Phe (3,5-F 2), Phe (4-CH 2 CO 2 H), Phe (penta -F), Phe (3,4-Cl 2), Phe (4-CF 3), Phe (4-OCH 3), Bip, Cha, 4- pyridyl alanine, βhTyr, OctGly, Phe (4- N ₃ ), Phe (4-Br), Phe [4- (2-aminoethoxy)] or Phe, Phe analogs, Tyr analogues or the corresponding? -Methyl amino acid forms of any of the foregoing; X11 is 2-Nal, 1-Nal, 2,4- dimethyl-Phe, Bip, Phe (3,4- Cl 2), Phe (3,4-F 2), Phe (4-CO 2 H), βhPhe ( 4-F), α-Me -Trp, 4- _{phenyl-cyclohexyl, Phe (4-CF 3)} , α-MePhe, βhNal, βhPhe, βhTyr, βhTrp, Nva (5- phenyl), Phe, His, hPhe, (4-OMe), Phe (4-Me), Trp (2,5,7-tri-tert-butyl), Phe ), Phe (4-tBu), Phe (4-guanidino, Phe (4-OBzl), Octgly, Glu (Bzl), 4-phenylbenzylalanine, Phe [4- 5-hydroxy--Trp, 6- chloro -Trp, N-MeTrp, 1,2,3,4- tetrahydro-Nord _{hareuman, Phe (4-CONH 2)} , Phe (3,4- dimethoxy), Phe _{(2,3-Cl 2), Phe} (2,3-F 2), Phe (4-F), 4- phenyl-cyclohexyl alanine, Bip, or the one of any of the corresponding methyl α- amino acid to form a; X12 is selected from the group consisting of His, Phe, Arg, N-Me-His, Val, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t- Me-Leu,? -MeOrn,? -MeSer,? -MeVal, Aib (Ac), Acvc, Acbc, Agp, Aib,? -Diethyl Gly,? -MeLys,? -MeLys , D-Ala, (D) Asn, (D) Asp, (D) Leu, (D) Phe, (D) Tyr, Aib,? -MeLeu,? -MeOrn,? -Aib, Glu, hArg, Ile, Lys, N-MeLeu, N-MeArg, Ogl, Orn, Pro, Gln, Ser, Thr, Tle, t-butyl- Gly, Lt; / RTI > amino acid form of any of < RTI ID = 0.0 > X13 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, Arg, Orn, Val,? HAla, Lys (Ac) Asp, Dlab, Dap,? -diethyl Gly, hLeu, Asn, Ogl, Pro, Gln, Asp, Cha, Chg, Asp, Dab, Dap,? -MeLeu, Aib,? -Ala,? -Glu,? hLeu,? hVal, , Ser,? -Spiro-pip, Thr, Tba, Tle or Aib, Cit, hArg, Lys, Asn, Orn, Gln or the corresponding? -Methylamino form of any of the foregoing; X14 is Phe, Tyr, Glu, Gly, His, Lys, Leu, Met, Asn, Pro, Gln, Arg, Ser, Thr, TicβhPhe, Arg, Lys Dap (Ac), Dab (Ac), Asp or the corresponding? -Methylamino form of any of the foregoing; Asp, (D) Leu, (D) Phe, (D) Thr, Aea, Asp, Asn, Glu, Glu, Ser, Thr, Gln, Ala, Phe, Gly, Lys, Leu, Pro, Arg, [beta] -Ala, Sarc, or the corresponding [alpha] -methyl amino acid forms of any of the foregoing; X16 is Asp, Glu, Ala, AEA, AEP,? HAla, Gaba, Gly, Ser, Pro, Asn, Thr or absent or the corresponding? -Methylamino form of any of the foregoing; X17 is Leu, Lys, Arg, Glu, Ser, Gly, Gln, or is absent or is the corresponding? -Methylamino acid form of any of the foregoing.

In certain embodiments of the peptide inhibitor of Xa, the bond is a disulfide bond, a thioether bond, a lactam bond, a triazole ring, a selenoether bond, a diselenide bond, or an olefin bond.

In certain embodiments of the peptide inhibitor of Xa, X4 is Cys, X9 is Cys, and the bond is a disulfide bond. In certain embodiments, X4 is Pen, X9 is Pen, and the bond is a disulfide bond. In certain embodiments: X7 is Trp; X10 is Phe, Tyr, Phe analogue, or Tyr analogue; X11 is Trp, 1-Nal or 2-Nal; X12 is Aib,? -Me-Lys, a-Me-Leu, Achc, Acvc, Acpc, Acbc or THP. In certain embodiments: X7 is Trp; X10 is Phe, Tyr, Phe analogue, or Tyr analogue; X11 is Trp, 1-Nal or 2-Nal; X12 is Aib,? -Me-Lys or a-Me-Leu. In certain embodiments, the peptide inhibitor comprises any of the following amino acid sequences: Pen-QTWQ-Pen- [Phe (4-OMe)] - [2-Nal] - [[alpha] -Me-Lys] -ENG; Pen-NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys (Ac)] - NN; Pen-QTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [? - MeLeu] - [Lys (Ac)] - NN; Or Pen-QTWQ- [Pen] - [ Phe (4-CONH 2)] - [2-Nal] - [α-MeLys] - [Lys (Ac)] - NN ( where the peptide inhibitor is between two amino acids Pen Lt; RTI ID = 0.0 > disulfide < / RTI >

In certain embodiments of the peptide inhibitor of Xa, X4 is an amino acid, aliphatic acid, alicyclic acid or a modified 2-methyl aromatic acid having a carbon side chain capable of forming a thioether bond with X9; X9 is a sulfur-containing amino acid capable of forming a thioether bond with X4, and the bond between X4 and X9 is a thioether bond. In certain embodiments, X4 is selected from the group consisting of Abu, 2-chloromethylbenzoic acid, methapto-propionic acid, methapto-butyric acid, 2-chloro-acetic acid, 3-chloro-propionic acid, 4-chloro-butyric acid, ; X9 is Abu, Cys, Pen, hCys, D-Pen, D-Cys, or D-hCys. In certain embodiments, X4 is Abu; X9 is Cys. In certain embodiments, X7 is Trp; X10 is Phe, Tyr, Phe analogue, or Tyr analogue; X11 is Trp, 1-Nal or 2-Nal; X12 is? -Me-Lys,? -Me-Leu,? -Me-Ser,? -Me-Val, Achc, Acvc, Acpc, Acbc, or [4-amino-4-carboxy-tetrahydropyran]. In certain embodiments, X7 is Trp; X10 is Phe, Tyr, Phe analogue, or Tyr analogue; X11 is Trp, 1-Nal or 2-Nal; X12 is? -Me-Lys or [4-amino-4-carboxy-tetrahydropyran]. In certain embodiments, the peptide inhibitor comprises any of the following amino acid sequences: [Abu] -QTWQC- [Phe (4-OMe)] - [2-Nal] - [[alpha] -MeLys] -E-N-G; [Abu] -Q-T-W-Q-C- [Phe (4- (2-aminoethoxy))] - W- [alpha -MeLys] -E-N-G; Or [Abu] -QTWQC- [Phe [4- (2-aminoethoxy)]] - [2-Nal] And a thioether bond between C).

In certain embodiments of the peptide inhibitor of Xa: X4 is Pen, Cys or hCys; X5 is any amino acid; X6 is any amino acid; X7 is Trp, Bip, Gln, His, Glu (Bzl), 4- benzyl alanine, Tic, Phe [4- (2- amino-ethoxy)], Phe (3,4-Cl 2), Phe (4- OMe), 5- hydroxy -Trp, 6- chloro -Trp, N-MeTrp, α- MeTrp, 1,2,3,4- tetrahydro-Nord _{hareuman, Phe (4-CO 2 H} ), Phe _{(4-CONH 2), Phe} (3,4- _{dimethoxy), Phe (4-CF 3} ), Phe (4-tBu), ββ-diPheAla, Glu, Gly, Ile, Asn, Pro, Arg, Thr , or Octgly, or the corresponding? -Methylamino form of any of the foregoing; X8 is any amino acid; X9 is Pen, Cys or hCys; X10 is selected from the group consisting of 1-Nal, 2-Nal, Aic, Bip, (D) Cys, Cha, DMT, (D) Tyr, Glu, Phe, His, Trp, Thr, Tic, Tyr, Phe Tyr analogue or analogues _{(optionally, Phe (3,4-F 2)} , Phe (3,4-Cl 2), F (3-Me), Phe [4- ( 2-aminoethoxy)], Phe [4- (2- (acetyl-amino-ethoxy)], Phe (4-Br ), Phe (4-CONH 2), Phe (4-Cl), Phe (4-CN), Phe (4- guanidyl dino), Phe (4-Me) , Phe (4-NH 2), Phe (4-N 3), Phe (4-OMe), or Phe (4-OBzl)), or wherein in any of the equivalent to what methyl α- amino acid form and; X11 is 2-Nal, 1-Nal, 2,4- dimethyl-Phe, Bip, Phe (3,4- Cl 2), Phe (3,4-F 2), Phe (4- _{CO 2 H), βhPhe (4} -F), α-Me-Trp, 4- _{phenyl-cyclohexyl, Phe (4-CF 3)} , α-MePhe, βhNal, βhPhe, βhTyr, βhTrp, Nva (5- phenyl) (4-O), Phe, His, hPhe, Tic, Tqa, Trp, Tyr, Phe ), Tyr (3-tBu), Phe (4-tBu), Phe (4-OBzl), Octgly, Glu (Bzl), 4-phenylbenzylalanine, Phe [4- - aminoethoxy)], 5-hydroxy-Trp, 6-chloro-Trp, N -MeTrp, 1,2,3,4- tetrahydro-Nord _{hareuman, Phe (4-CONH 2)} , Phe (3,4-OMe 2) Phe (2,3-Cl 2), Phe (2,3- _{F 2), Phe (4-} F), 4- phenyl-cyclohexyl alanine or Bip, or methyl, and α- amino acids form corresponding of any of the above; X12 is α-MeLys, α-MeOrn, α-MeLeu, α (D) Asn, (D) Leu, (D) Asp, (D) Asp, (D) Asp, Phe, Phe, Cha, Chg, Asp, Dab, Dap,? -Diethyl Gly, Glu, Phe , hLeu, hArg, hLeu, Ile, Lys, Leu, Asn, N-MeLeu, N-MeArg, Ogl, Orn, Pro, Gln, Arg, Ser, Thr or Tle, Amino acid form; X13 is selected from the group consisting of Lys (Ac), (D) Asn, (D) Leu, (D) Thr, (D) Phe, Ala, Aib,? -MeLeu,? -Ala,? HGlu,? HAla,? HLeu, Gly, Phe, hLeu, Lys, Leu, Asn, Ogl, Pro, Gln, Asp, Arg, Ser, Spiro, Phe, Cha, Chg, Asp, Lys, Arg, Orn, Dab, Dap, -pip, Thr, Tba, Tlc, Val or Tyr, or the corresponding? -methylamino form of any of the foregoing; X14 is selected from the group consisting of Asn, Glu, Phe, Gly, His, Lys, Leu, Met, Asn, Pro, Gln, Arg, Ser, Thr, Tic or Tyr, Lys Methyl amino acid form; Asp, Asn, (D) Leu, (D) Phe, (D) Thr, Ala, AEA, Asp, Glu, Phe, Gly, Lys, Leu, Pro, Gln, Arg or Ser, [beta] -Ala, Arg or the corresponding [alpha] -methyl amino acid forms of any of the foregoing; X16 is absent or is the corresponding? -Methylamino form of any of Gly, Ala, Asp, Ser, Pro, Asn or Thr, or any of the foregoing; X17 is absent or is the corresponding? -Methylamino form of Glu, Ser, Gly or Gln, or any of the foregoing; X18 is absent, or is any amino acid; X19 is absent or is any amino acid; X20 is absent or is any amino acid. In certain embodiments, the bond between X4 and X9 is a disulfide bond. In certain embodiments, X1, X2, and X3 are absent. In certain embodiments, X17, X19, and X20 are absent. In certain embodiments, either X4 or X9, or both, is Pen. In certain embodiments, X4 and X9, both of which are Pen. In certain embodiments, X 18 is (D) -Lys. In certain embodiments, the peptide inhibitor comprises one or more, two or more, three or more of the following: X5 is Arg, Asn, Gln, Dap, Orn; X6 is Thr or Ser; X7 is selected from Trp, 2-Nal, 1-Nal, Phe (4-Olyl), Tyr (3-tBu), Phe (4-tBu), Phe 4-Me), 5-hydroxy-Trp, 6-chloro-Trp, N-MeTrp, a-MeTrp or 1,2,3,4-tetrahydro-norharmane; X8 is Gln, Val, Phe, Glu, Lys. In certain embodiments, the peptide inhibitor comprises one or more, two or more, three or more, or four or more, five or more, six or more, seven of the following: X10 is Tyr, Phe (4- ), Phe (4-OMe) , Phe (4-CONH 2), Phe (3,4-Cl 2), Phe (4-tBu), Phe (4-NH 2), Phe (4-Br), Phe (4-CN), Phe (4-CO ₂ H), Phe (4- (2-aminoethoxy)) or Phe (4-guanadino); X11 is selected from Trp, 2-Nal, 1-Nal, Phe (4-Olyl), Tyr (3-tBu), Phe (4-tBu), Phe 4-Me), 5-hydroxy-Trp, 6-chloro-Trp, N-MeTrp, a-MeTrp or 1,2,3,4-tetrahydro-norharmane; X12 is Arg,? -MeLys? -MeLeu, Aib or? -MeOrn; X13 is Lys, Glu or Lys (Ac); X14 is Phe or Asn; X15 is GIy, Sr or Ala; X16 is absent, or AEA. In certain embodiments, X4 and X9 are Pen; X5 is Gln; X6 is Thr; X7 is Trp; X8 is Gln; X10 is Tyr, Phe (4-OMe) or 2-Nal; X11 is Trp, 2-Nal or 1-Nal; X12 is Arg,? MeLys or? -MeOrn; X13 is Lys, Glu or Lys (Ac); X14 is Phe or Asn; X15 is GIy; X16 does not exist. In certain embodiments, no more than one of Xl, X2, and X3 is present and no more than one, two or more, three or four of X17, X18, X19, and X20 are present.

In certain embodiments of the peptide inhibitor of Xa: X4 is Abu, Pen, or Cys; X7 is Trp, Bip, Gln, His, Glu (Bzl), 4- benzyl alanine, Tic, Phe [4- (2- amino-ethoxy)], Phe (3,4-Cl 2), Phe (4- OMe), 5- hydroxy -Trp, 6- chloro -Trp, N-MeTrp, α- MeTrp, 1,2,3,4- tetrahydro-Nord _{hareuman, Phe (4-CO 2 H} ), Phe (4 -CONH _2), Phe (3,4- _{dimethoxy), Phe (4-CF 3} ), ββ- di PheAla, Phe (4-tBu) , Glu, Gly, Ile, Asn, Pro, Arg, Thr or Octgly , Or the corresponding? -Methylamino form of any of the foregoing; X9 is Abu, Pen, or Cys; X10 is selected from the group consisting of 1-Nal, 2-Nal, Aic, Bip, (D) Cys, Cha, DMT, (D) Tyr, Glu, Phe, His, Trp, Thr, Tic, Tyr, Analog or Tyr analog, or the corresponding? -Methyl amino acid form of any of the foregoing; X11 is selected from the group consisting of 2-Nal, 1-Nal, 2,4-dimethyl Phe, Bip, 4-phenylcyclohexyl, Glu (Bzl), 4-phenylbenzylalanine, Tic, Phe [4- (2-aminoethoxy) _{, Phe (3,4-Cl 2)} , Phe (3,4-F 2), βhPhe (4-F), Phe (4-OMe), 5- hydroxy -Trp, 6- chloro -Trp, N- MeTrp,? -MeTrp, 1,2,3,4-tetrahydro-norharmane, Phe (4-CO ₂ H), Phe (4-CONH ₂ ), Phe (3,4-dimethoxy) _{-CF 3), Phe (2,3-} Cl 2), Phe (2,3-F 2), Phe (4-F), 4- phenyl-cyclohexyl-alanine, α-MePhe, βhNal, βhPhe , βhTyr, βhTrp Phe (4-O-allyl), Bip, Nva (5-phenyl), Phe, His, hPhe, Tqa, Trp, Tyr, Phe , Tyr (3-tBu), Phe (4-tBu), Phe (4-guanidino), Phe (4-OBzl), or Octgly or the corresponding? -Methyl amino acid forms of any of the foregoing; (D) Asp, (D) Asp, (D) Phe, (D) Thr, 3-MeLys, Asp, Dab, Dap,? -Diethyl Gly, Glu, Phe, hLeu, hArg, hLeu, Ile,? -Hal,? HAe,? HLeu,? HVal,? -Spiro-pip, Cha, Chg, Asp, Dab, Dap, Lys, Leu, Asn, N-MeLeu, N-MeArg, Ogl, Orn, Pro, Gln, Arg, Ser, Thr or Tle or the corresponding? -Methylamino form of any of the foregoing; X13 is Lys (Ac), (D) Asn, (D) Leu, (D) Thr, (D) Phe, Ala, Aib,? -MeLeu,? Ala,? HGlu,? HAla,? HLeu,? HVal, , Cha, Chg, Asp, Arg, Orn, Dab, Dap,? -Diethyl Gly, Glu, Phe, hLeu, Lys, Leu, Asn, Ogl, Pro, Gln, Asp, Arg, Ser, , Tba, TIc, Val or Tyr, or the corresponding [alpha] -methyl amino acid forms of any of the foregoing; X14 is a corresponding? -Methyl amino acid form of any of the foregoing, or Asn, Glu, Phe, Gly, His, Lys, Leu, Met, Asn, Pro, Gln, Arg, Ser, Thr, Tic or Tyr; Asp, Asn, (D) Leu, (D) Phe, (D) Thr, Ala, AEA, Asp, Glu, Phe, Gly, Lys, (D) Ala, (D) Asn, (D) Asp, Asn, (D) Leu, Pro, Gln, Arg or Ser, or the corresponding a-methyl amino acid forms of any of the above. Leu, (D) Phe, (D) Thr, Ala, Asn, Ser, AEA, Asp, Glu, Phe, Gly, Lys, Leu, Pro, Gln, Arg or Ser, Methyl amino acid form; X16 is absent or is the corresponding? -Methylamino form of any of Gly, Ala, Asp, Ser, Pro, Asn or Thr, or any of the foregoing; X17 is absent or is a form of Glu, Ser, Gly or Gln, or the corresponding [alpha] -methyl amino acid of any of the above. In certain embodiments, the peptide inhibitor is cyclized via an intramolecular bond between X4 and X9. In certain embodiments, no more than one of Xl, X2 and X3 is present. In certain embodiments, no more than one of X17, X19, and X20 is present. In certain embodiments, one of X4 or X9 is Abu and the other of X4 or X9 is not Abu. In certain embodiments, the peptide inhibitor comprises one or more, two or more, three or more, or four of the following: X5 is Arg, Gln, Dap or Orn; X6 is Thr or Ser; X7 is selected from the group consisting of Trp, 2-Nal, 1-Nal, Phe (4-Olyl), Tyr (3-tBu), Phe Phe (4-Me), 5-hydroxy-Trp, 6-chloro-Trp, N-MeTrp, or? -MeTrp, 1,2,3,4-tetrahydro-norharmane; X8 is Gln, Val, Phe, Glu or Lys. In certain embodiments, the peptide inhibitor comprises one or more, two or more, three or more, or four or more, five or more, six or more, seven of the following: X10 is Tyr, Phe (4- ), Phe (4-OMe) , Phe (4-CONH 2), Phe (3,4-Cl 2), Phe (4-tBu), Phe (4-NH 2), Phe (4-Br), Phe (4-CN), Phe (4-CO ₂ H), Phe (4- (2-aminoethoxy)) or Phe (4-guanadino); X11 is selected from Trp, 2-Nal, 1-Nal, Phe (4-Olyl), Tyr (3-tBu), Phe (4-tBu), Phe 4-Me), 5-hydroxy-Trp, 6-chloro-Trp, N-MeTrp, a-MeTrp or 1,2,3,4-tetrahydro-norharmane; X12 is Arg, hLeu, (D) Asn, Aib,? -MeLys,? -MeLeu or? -MeOrn; X13 is Lys, Glu or Lys (Ac); X14 is Phe or Asn; X15 is GIy, Ser or Ala, or X15 is Asn, GIy, Ser, betaAla or Ala; X16 is absent, or AEA.

In certain embodiments of any of the peptide inhibitors: X4 and X9 are Pen. In certain embodiments, X4 and X9 form a disulfide bond.

In certain embodiments, X4 is Abu and X9 is Cys. In certain embodiments, X4 and X9 form a thioether linkage.

In certain embodiments, the peptide inhibitor comprises an amino acid sequence of any of SEQ ID NOs: 365 to 370, 857 to 1029. In certain embodiments, the peptide inhibitor is cyclized through a bond between X4 and X9, and the peptide inhibitor inhibits the binding of interleukin-23 (IL-23) to the IL-23 receptor.

(Vf), (Vg), and (Vh), (Vb), (Vc), Lt; RTI ID = 0.0 > of < / RTI >

In certain embodiments of the peptide inhibitor of Xa: the peptide inhibitor comprises any of the following amino acid sequences:

[Palm] - [Iso Glu] - [PEG4] - [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys Ac)] - < / RTI &_gt;NNNH2;

Ac- [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys (PEG4- NH ₂ ;

Ac- [Pen] -QTWQ- [Pen] -Phe (4-CONH 2) - [2-Nal] - [α-MeLys (Ac)] - [Lys (Ac)] - NN-NH 2;

[Octyl] - [iso Glu] - [PEG4] - [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys (Ac)] - NN-NH 2;

(Ac)] - [2-Nal] - [Aib] - [PEG4] - [Pen] -NTWQ- [Pen] - [Phe 4- (2-aminoethoxy) NN-NH _2;

[Palm] - [PEG4] - [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] -NH ₂ ;

Ac- [Pen] -NTWQ- [Pen] - [Phe [4- ( 2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys (PEG4- octa-carbonyl)] - NN-NH ₂ ;

Ac- [Pen] -NTWQ- [Pen] - [Phe [4- ( 2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys (PEG4-Palm)] - NN-NH 2;

Ac- [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy) - (PEG4- Palm)] - [2-Nal] - [Aib] NH ₂ ;

Ac- [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy) - (PEG4-lauryl)] - [2-Nal] - [Aib] NN-NH _2;

Ac- [Pen] -QTWQ- [Pen] -Phe (4-CONH 2) - [2-Nal] - [α-MeLys (PEG4-Palm) - [Lys (Ac)] - NN-NH 2;

Ac- [Pen] -QTWQ- [Pen] -Phe (4-CONH 2) - [2-Nal] - [α-MeLys (PEG4- lauryl)] - [Lys (Ac) ] - NN-NH 2;

Ac- [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy) - (PEG4-iso Glu- Palm)] - [2-Nal] - [Aib] ] -NN-NH _2;

Ac- [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy) - (PEG4-iso Glu-lauryl)] - [2-Nal] - [Aib] )] - NN-NH _2;

Ac- [Pen] -QTWQ- [Pen] -Phe (4-CONH 2) - [2-Nal] - [α-MeLys (PEG4- iso-Glu-Palm)] - [Lys (Ac)] - NN-NH ₂ ;

Ac- [Pen] -QTWQ- [Pen] -Phe (4-CONH 2) - [2-Nal] - [α-MeLys (PEG4- isopropyl Glu- lauryl)] - [Lys (Ac) ] - NN- NH ₂ ;

Ac- [Pen] -QTWQ- [Pen] -Phe (4-CONH 2) - [2-Nal] - [α-MeLys (IVA)] - [Lys (Ac)] - NN-NH 2;

Ac- [Pen] -QTWQ- [Pen] -Phe (4-CONH 2) - [2-Nal] - [α-MeLys ( Biotin)] - [Lys (Ac) ] - NN-NH 2;

Ac- [Pen] -QTWQ- [Pen] -Phe (4-CONH 2) - [2-Nal] - [α-MeLys ( octa-carbonyl)] - [Lys (Ac) ] - NN-NH 2;

Ac- [Pen] - [Lys (IVA)] - TWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] NN-NH _2;

Lys (Ac)] - [Lys (IVA)] - [2-Nal] - [Aib] N-NH _2;

Ac- [Pen] - [Lys (Biotin)] - TWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] NN-NH _2;

Ac- [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys (Ac)] - [Lys N-NH _2;

Ac- [Pen] - [Lys (octanyl)] - TWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] -NN-NH _2;

Ac- [Pen] -NTWQ- [Pen] - [Phe 4- (2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys (Ac)] - [Lys (octanyl) -N-NH _2;

Ac- [Pen] - [Lys (Palm)] - TWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] -NN-NH _2;

Ac- [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys -NH ₂ ;

Ac- [Pen] - [Lys (PEG8)] - TWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] NN-NH _2;

Ac- [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys (Ac)] - [Lys (PEG8) N-NH _2;

[Ac] - [Lys (Ac)] - NN [Ac- [Pen] -K (Pegl1-Palm) TWQ- [Pen] - [Phe 4- -NH ₂ ;

Ac- [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys (Ac)] - [Lys )] - N-NH _2;

Ac- [Pen] - [Cit] -TW- [Cit] - [Pen] - [Phe 4- (2-aminoethoxy)] - [2- ] -NN-NH _2;

Ac- [Pen] - [Lys (Ac)] - TW- [Cit] - [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] _{Ac)] - NN-NH 2} ;

[Ac-Phe] -NT- [Phe (3,4-OCH3) 2] -Q- [Pen] - [Phe [4- (2-aminoethoxy)] - [2- [Lys (Ac)] - NN -NH 2;

[2-Nal] - [Aib] - [Phe] [4- (2-aminoethoxy)] - [2- [Lys (Ac)] - NN -NH 2;

Ac- [Pen] -NT- [Phe (3-CH3)] - Q- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] _{Ac)] - NN-NH 2} ;

[Ac- [Pen] -NT- [Phe (4-CH3)] - Q- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] _{Ac)] - NN-NH 2} ;

Ac [(D) Arg] - [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [βAla] -NH _2;

Ac - [(D) Tyr] - [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] N- [βAla] -NH _2;

Ac- [Pen] -NTWQ- [Pen] - [Phe [4- ( 2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys (Ac)] - QN-NH 2;

Ac- [Pys] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys N-NH _2;

(Ac) - [Lys (Ac)] - [Lys (Ac)] - [Phen] -NTWQ- [Pen] - [Phe 4- (2-aminoethoxy)] - [2- ] -NH _2;

Ac- [Pen] -NTWQ- [Pen] - [Phe [4- ( 2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys (Ac)] - QQ-NH 2;

Ac- [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys ;

Ac- [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys ₂ ;

Ac- [Pen] -NTWQ- [Pen] - [Phe [4- ( 2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys (Ac)] - [Cit] -NNH 2;

Ac- [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys ₂ ;

Ac- [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys Ac)] - NH _2;

Ac- [Pys] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys [Cit] -NH _2;

Ac- [Pen] -NTWQ- [Pen] - [Phe [4- ( 2-aminoethoxy)] - [2-Nal] - [Aib] -QN- [βAla] -NH 2;

Ac- [Pen] -NTWQ- [Pen] - [Phe [4- ( 2-aminoethoxy)] - [2-Nal] - [Aib] -E- [Cit] -Q-NH 2;

Ac- [Pen] -NTWQ- [Pen] - [Phe [4- ( 2-aminoethoxy)] - [2-Nal] - [Aib] - [Cit] -N- [Cit] -NH 2;

Ac- [Pen] -NTWQ- [Pen] - [Phe [4- ( 2-aminoethoxy)] - [2-Nal] - [Aib] - [Cit] -Q- [Cit] -NH 2;

(Ac) - NN-NH- [Phe] [4- (2-aminoethoxy)] - [2-Nal] - [Aib] ₂ ;

Ac- [Pen] -NTWQ- [Pen] - [Phe [4- ( 2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys (Ac)] - NN-NH 2;

Ac- [Pen] -NTWQ- [Pen] - [Phe [4- ( 2-aminoethoxy)] - [2-Nal] - [Aib] -QNN-NH 2;

Ac- [Pen] -NTWQ- [Pen] - [Phe [4- ( 2-aminoethoxy)] - [2-Nal] - [Aib] -ENQ-NH 2;

Ac- [Pen] -GPWQ- [Pen] - [Phe [4- ( 2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys (Ac)] - NN-NH 2;

Ac- [Pen] -PGWQ- [Pen] - [Phe [4- ( 2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys (Ac)] - NN-NH 2;

Ac- [Pen] -NTWN- [Pen] - [Phe [4- ( 2- amino)] - [-2 Nal] - [Aib] - [Lys (Ac)] - NN-NH _2;

Ac- [Pen] -NSWQ- [Pen] - [Phe [4- ( 2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys (Ac)] - NN-NH 2;

(Ac) -NN [Aib] -WQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] -NH ₂ ;

Ac- [Pen] -NTW- [Aib] - [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys ] -NH _2;

[Ac] - [Lys (Ac)] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] NN-NH _2;

Ac- [Pen] - [Lys (Ac)] - TWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2- NNNH ₂ ;

Ac- [Pen] -QVWQ- [Pen] - [Phe [4- ( 2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys (Ac)] - NN-NH 2;

Ac- [Pen] -NT- [2-Nal] -Q- [Pen] - [Phe [4- (2-aminoethoxy)] - [2- -NN-NH _2;

Ac- [Pen] -NT- [1-Nal] -Q- [Pen] - [Phe 4- (2-aminoethoxy)] - [2-Nal] - [Aib] -NN-NH _2;

Ac- [Pen] -NTWQ- [Pen] - [Phe [4- ( 2-aminoethoxy)] - [2-Nal] - [α-MeLeu] - [Lys (Ac)] - NN-NH 2;

Ac- [Pen] -NTWQ- [Pen] - [Phe [4- ( 2-aminoethoxy)] - [2-Nal] - [α-MeLys] - [Lys (Ac)] - NN-NH 2;

Ac- [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] )] - NN-NH _2;

Ac- [Pen] -NTWQ- [Pen] - [Phe 4- (2-aminoethoxy)] - [2-Nal] - [α- MeLeu] - [Lys -NH ₂ ;

Ac- [Pen] -NTWQ- [Pen] - [Phe 4- (2-aminoethoxy)] - [2-Nal] - [ -NH ₂ ;

Ac- [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] )] - N- [βAla] -NH 2;

Ac- [Pen] -NTWQ- [Pen] - [Phe [4- ( 2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys (Ac)] - LN-NH 2;

Ac- [Pen] -NTWQ- [Pen] - [Phe [4- ( 2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys (Ac)] - GN-NH 2;

Ac- [Pen] -NTWQ- [Pen] - [Phe [4- ( 2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys (Ac)] - SN-NH 2;

Ac- [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys ₂ ;

Ac- [Pen] -NTWQ- [Pen] - [Phe [4- ( 2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys (Ac)] - FN-NH 2;

(Ac) - NN-NH- [Pen] -NTW- [Cit] - [Pen] - [Phe 4- (2-aminoethoxy)] - [2-Nal] - [Aib] ₂ ;

Ac- [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys -NH ₂ ;

Ac- [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys (Ac)] - [nLeu] -NH ₂ ;

Ac- [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys ₂ ;

Ac- [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys ₂ ;

Ac- [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys NH ₂ ;

Ac- [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys NH ₂ ;

Ac- [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys NH ₂ ;

Ac- [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys ] -NH _2;

Ac- [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys (Ac)] - [N-MeAla] [βAla] -NH _2;

Ac- [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys βAla] -NH _2;

Ac- [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys ₂ ;

- [2-Nal] - [4-amino-4-carboxy-tetrahydrobenzo [ pyran] - [Lys (Ac)] NNNH 2;

[2-Nal] - [4-amino-4-carboxy-tetrahydropyran] -ENN [Phe] -NH ₂ ;

(Ac) -cyclo [[Abu] -QTWQC] - [Phe [4- (2-aminoethoxy)] - [2-Nal] ] -NN-NH _2;

- [2-Nal] - [4-amino-4-carboxy-tetrahydropyran-4-yl] ] - [Lys (Ac)] - NN-NH 2;

- [2-Nal] - [4-amino-4-carboxy-tetrahydropyran-4-yl] ] - [Lys (Ac)] - NN-NH 2;

Ac-E - [(D) Arg] -cyclo [[Abu] -QTWQC] - [Phe [4- (2-aminoethoxy)] - [2- tetrahydropyran] -ENN-NH _2;

- [2-Nal] - [4-amino-isoquinolin-2-yl] - [ 4-carboxy-tetrahydropyran] -ENN-NH _2;

Ac-R - [(D) Arg] -cyclo [[Abu] -QTWQC] - [Phe [4- (2-aminoethoxy)] - [2- tetrahydropyran] -ENN-NH _2;

Ethoxy- Eno)] - [2-Nal] - [4- amino-4-carboxy-tetrahydropyran] -ENN-NH _2;

Ac-F - [(D) Arg] -cyclo [[Abu] -QTWQC] - [Phe [4- (2-aminoethoxy)] - [2- tetrahydropyran] -ENN-NH _2;

[(2-Nal) - [4-Amino-2-amino-isoquinoline- 4-carboxy-tetrahydropyran] -ENN-NH _2;

[2-Nal] - [4-Amino-4 (2-amino) ethoxy] - [2-Nal] - [(D) Arg] -cyclo [[Abu] -QTWQC] - carboxy-tetrahydropyran] -ENN-NH _2;

Ac-T - [(D) Arg] -cyclo [[Abu] -QTWQC] - [Phe [4- (2-aminoethoxy)] - [2- tetrahydropyran] -ENN-NH _2;

Ac-L - [(D) Arg] -cyclo [[Abu] -QTWQC] - [Phe [4- (2-aminoethoxy)] - [2- tetrahydropyran] -ENN-NH _2;

- [2-Nal] - [4-amino-isoxazol-4-yl] - [ 4-carboxy-tetrahydropyran] -ENN-NH _2;

- [2-Nal] - [4-amino-isoquinolin-2-yl] - [ 4-carboxy-tetrahydropyran] -ENN-NH _2;

- [2-Nal] - [4-amino-4-carboxy-tetrahydropyran] - [Phe [4- (2-aminoethoxy) - (PEG4-Alexa488)] - -ENN-NH _2;

[Alexa 488] - [PEG 4] -cyclo [[Abu] -QTWQC] - [Phe [4- (2-aminoethoxy)] - [2-Nal] ] -ENN-NH _2;

[Phe] [4- (2-aminoethoxy)] - [2-Nal] - [4-amino-4- carboxy-tetrahydropyran- -ENN-NH _2;

[Phe [4- (2-aminoethoxy)] - [2-Nal] - [4-amino 4-carboxy-tetrahydropyran] - [Lys (Ac)] - NN-NH 2;

- [Phe [4- (2-aminoethoxy)] - [2-Nal] - [4-amino-4- - carboxy-tetrahydropyran] - [Lys (Ac)] - NN-NH 2; And

- [Phe [4- (2-aminoethoxy)] - [2-Nal] - [4-amino-4- - carboxy-tetrahydropyran] - [Lys (Ac)] - NN-NH 2,

Wherein the peptide inhibitor is cyclized via a disulfide bond between two Pen residues or via a thioether bond between the Abu and Cys residues and the peptide inhibitor is an IL-23 receptor of interleukin-23 (IL-23) .

In certain embodiments, any of the peptide inhibitors described herein comprise one or more half-life extension moieties conjugated to the peptide inhibitor and / or one or more linker moieties. In certain embodiments, the half-life extension moiety is conjugated to the peptide inhibitor via one or more linker moieties.

In certain embodiments, any of the peptide inhibitors described herein further comprises a conjugated chemical substituent. In certain embodiments, the conjugated chemical substituents are lipophilic substituent or polymeric moiety, for example, Ac, Palm, Palm gamma-Glu, Glu-isopropyl Palm, PEG2-Ac, PEG4- iso Glu-Palm, (PEG) ₅ -Palm, succinic acid, glutaric acid, pyroglutamic acid, benzoic acid, IVA, octanoic acid, 1,4-diaminobutane, isobutyl or biotin. In certain embodiments, the conjugated chemical substituent is a polyethylene glycol having a molecular mass of 400 Da to 40,000 Da.

In another aspect, the invention includes a peptide inhibitor, or a pharmaceutically acceptable salt or solvate thereof, comprising a structure of formula (I): < EMI ID =

R ¹ -XR ² (I)

In this formula,

R ¹ is selected from the group consisting of a bond, hydrogen, C 1 -C 6 alkyl, C 6 -C 12 aryl, C 6 -C 12 aryl, C 1 -C 6 alkyl, C 1 -C 20 alkanoyl, and the PEGylated version of any of the foregoing, ≪ / RTI >

R ² is a bond, OH or NH ₂ ;

X is any of the peptide sequences described herein, such as Xa, I, Ia-It, II, IIa-IId, III, IIIa-IIIe, IV, IVa-IVb, V, or Va-Vh.

In a related aspect, the invention provides a peptide dimer inhibitor of an interleukin-23 receptor, wherein the peptide dimer inhibitor comprises two peptide monomer subunits linked via one or more linker moieties, wherein each peptide monomer subunit RTI ID = 0.0 > interleukin-23 < / RTI > receptor, wherein the peptide has a sequence or structure as described herein. In certain embodiments, one or both of the peptide monomer subunits are cycled through intramolecular bonds between X4 and X9. In certain embodiments, one or both of the intramolecular bonds is a disulfide bond, a thioether bond, a lactam bond, a selenoether, a diselenide, or an olefin bond. In certain embodiments, the linker is any of those set forth in Table 2 or below. In certain embodiments, the linker moiety is a diethylene glycol linker, an iminodiacetic acid (IDA) linker, a beta -Ala-iminodiacetic acid (beta -Ala-IDA) linker, or a PEG linker. In certain embodiments, the N-terminus of each peptide monomer subunit is joined by a linker moiety. In certain embodiments, the C-terminus of each peptide monomer subunit is linked by a linker moiety. In certain embodiments, the linker connects the internal amino acid residue of at least one of the peptide monomer subunits to the N-terminus, C-terminus, or internal amino acid residue of the other peptide monomer subunit.

In a further related aspect, the invention includes polynucleotides comprising a peptide inhibitor of the invention or a sequence encoding one or both of the peptide monomer subunits of the inventive peptide dimer inhibitor. The present invention also includes a vector comprising a polynucleotide.

In another aspect, the invention includes a pharmaceutical composition comprising a peptide inhibitor or a peptide dimer inhibitor of the invention, and a pharmaceutically acceptable carrier, excipient, or diluent. In certain embodiments, the pharmaceutical composition comprises an enteric coating. In certain embodiments, the enteric coating protects and releases the pharmaceutical composition within the lower gastrointestinal tract of the subject.

In another aspect, the invention provides a method of treating a condition selected from the group consisting of inflammatory bowel disease (IBD), ulcerative colitis, Crohn's disease, celiac disease ( non-tropical Sprue), serum response chapters related arthropathy of voice disorders, fine colitis, collagen colitis, eosinophilic gastroenteritis, colitis associated with chemotherapy or radiation therapy, leukocyte adhesion deficiency-1, chronic granulomatosis, glycogen accumulation disease type 1b, Colitis associated with congenital immunity, such as in Hermansky-Pudlak syndrome, Chediak-Higashi syndrome, and Wiskott-Aldrich syndrome, , Gastrointestinal cancer, pancreatitis, insulin-dependent diabetes mellitus, mastitis, cholecystitis, cholangitis, biliary tract inflammation, chronic bronchitis, chronic sinusitis, asthma, psoriasis, or graft versus host disease caused by colonic resection and ileoanal anatomosis Include, but are not limited to, methods of treating or preventing diseases associated with IL-23 signaling. In certain embodiments, the inflammatory bowel disease is ulcerative colitis or Crohn's disease. In certain embodiments, the peptide inhibitor or peptide dimer inhibitor inhibits the binding of interleukin-23 (IL-23) to the interleukin-23 receptor (IL-23R). In certain embodiments, the pharmaceutical composition is administered orally, intravenously, intraperitoneally, intradermally, subcutaneously, intramuscularly, intraspinally, by inhalation, by vapourisation, spraying, sublingual, buccal, parenteral, rectal, Is provided to the subject by a topical route of administration. In certain embodiments, the pharmaceutical composition is provided orally for the treatment of inflammatory bowel disease (IBD), ulcerative colitis, Crohn's disease. In certain embodiments, the pharmaceutical composition is provided topically, parenterally, intravenously, subcutaneously, intraperitoneally, or intravenously to a subject for psoriasis treatment.

1 , An example of a rat IL-23 dose-response curve, measured at the level of IL-17A in a rat spleen cell assay, is provided.
Figure 2 is a graph showing IL-12-dependent production of IFNy from human PBMCs treated with the indicated amounts of Compound A or Compound B;
Figure 3 shows the results for the DAI value at day 7. Statistical analysis of significance was determined using a Student's t-test (GraphPad Prism). Differences were recognized significantly. * p <0.05, ** p <0.01, *** p <0.001, **** p <0.0001.
Figure 4 shows the sequence of amino acid sequences of human IL-23R, mouse IL-23R, rat IL-23R, chimpanzee IL-23R, IL-23R and IL-23R, wherein highly conserved amino acid residues Is displayed. The regions of the murine IL-23R that are not present in the other IL-23R species presented are shown, and the region of IL-23R that the particular peptide inhibitor of the present invention is able to bind is indicated by the dotted line.
Figure 5 is a table outlining the study design for TNBS induced colitis in rats.
Figures 6a-6d are graphs showing the weight of the colon versus the length (Figure 6a), the thickness of the colon wall (Table 6b), the length of the colon after treatment with vehicle (s) The graph shows the amount of myeloperoxidase (MPO) present in the proximal colon extract quantitated by visual inspection (visual score) (Table 6c) or ELISA. Values are presented as means ± SD. Statistical significance assessment by member ANOVA: * ≤0.05; **? 0.01; *** p? 0.001; **** p? ns.
FIG. 7 shows the results of the immunohistochemical staining for anti-IL-23p19 antibody (left top panel), vehicle treatment (transmural inflammation, presence of necrotic tissue and mucosa free of cypts) (Left lower panel), or 160 mg / kg / d Compound C (lesion appears to be restricted to mucosa only) (right lower panel).
Figures 8A-8E show the effects of vehicle treatment, anti-IL-23p19 antibody treatment, or inflammation (Figure 8a), mucosal necrosis (Figure 8b), gland loss (Figure 8c) Wall thickness (Fig. 8d) and histological score (Fig. 8e).
Figure 9 shows the concentration of compound C in the plasma and proximal colon (left panel), and the rat splenocyte assay (middle panel) and the rat IL-23R ELISA assay (right panel) measured 1 hour after the final PO dosing Lt; RTI ID = 0.0 &gt; IC75 < / RTI &gt;
Figure 10 shows the structure of a particular peptide inhibitor and provides a schematic illustrating a representative binding pattern between X4 and X9.
Figures 11A-11E show pharmacokinetic data for peptide 993 (SEQ ID NO: 993), an IL-23R peptide inhibitor. Figure 11A shows the concentration of peptide 993 in serum (nM) specified at different time points up to 24 hours after oral administration of peptide 993. Figures 11B-11D show the concentration of peptide 993 (nM) in samples taken from the Peyer's Patch (Figure 11B), small intestine (Figure 11C), and colon (Figure 11D). The dotted line represents 350 mM. FIG. 11E shows the amount (% by volume) of peptide 993 measured during feces at 24 hours after oral administration.
Figures 12A-12D summarize experiments comparing the treatment of peptide 993 with systemic treatment with prednisolone or anti-IL-23p19 neutralizing antibody and oral administration in a TNBS model of acute colitis. Figure 12A shows weight change (%) from 0 day to 7 days in simulated, vehicle and peptide 993 treated rats. Figure 12B shows the colon weight to colon length ratio (mg / cm) of the colon collected in rats at 7 days. Figure 12C shows the colon visually the colon score of the colon collected in the rat at 7 days. Figure 12D shows the sum of histopathological scores for the colon taken from simulated, vehicle and peptide 993 treated rats. For all experiments, statistical comparisons between groups were performed after 1-Way ANOVA followed by post-test: * p <0.05; ** p &lt;0.01; *** p &lt;0.001; **** p <0.0001; ns, not significant.
Figures 13A-13C summarize experiments comparing the treatment of peptide 1185 with systemic treatment with prednisolone or anti-IL-23p19 neutralizing antibody and oral administration in a TNBS model of acute colitis. Figure 13A shows the body weight change (%) from 0 days to 7 days in simulated, vehicle and peptide 1185 treated rats. Fig. 13B shows the colon weight to colon length ratio (mg / cm) of the colon collected in rats at 7 days. Figure 13C shows the colon visually the colon score collected in the rats at 7 days. For all experiments, statistical comparisons between groups were performed after 1-Way ANOVA followed by post-test: * p <0.05; ** p &lt;0.01; *** p &lt;0.001; **** p <0.0001; ns, not significant.
14A-14D summarize experiments comparing the treatment of peptide 980 with systemic treatment with prednisolone or anti-IL-23p19 neutralizing antibody in a TNBS model of acute colitis by oral administration. Figure 14A shows the weight change (%) from 0 to 7 days in simulated, vehicle and peptide 980 treated rats. 14B shows the colon weight to colon length ratio (mg / cm) of the colon collected in the rat at 7 days. Figure 14C shows the colon visually the colon score of the colon collected in the rat at 7 days. Figure 14D shows the sum of histopathological scores for colon collected from simulated, vehicle and peptide 980 treated rats. For all experiments, statistical comparisons between groups were performed after 1-Way ANOVA followed by post-test: * p <0.05; ** p &lt;0.01; *** p &lt;0.001; **** p <0.0001; ns, not significant.
Figures 15A-15E show the disease levels of the rats from the simulated (TNBS-unexposed) experimental group, or the TNBS-exposed experimental group treated with vehicle or peptide 993 and the measured IL-23 indicated biomarker levels in the colon will be. Data for MPO (Figure 15A), IL-6 (Figure 15B), IL-1 beta (Figure 15C), IL-22 (Figure 15D), and IL-17A (Figure 15E). For all experiments, statistical comparisons between groups were performed after 1-Way ANOVA followed by post-test: * p <0.05; ** p &lt;0.01; *** p &lt;0.001; **** p <0.0001; ns, not significant.
Figures 16A-16B show the disease levels of rats from the simulated (TNBS-unexposed) experimental group, or the TNBS-exposed experimental group treated with vehicle or peptide 980, and the measured IL-23 indicated biomarker levels in the colon It shows. MPO (Fig. 16A) and IL-22 (Fig. 16B). For all experiments, statistical comparisons between groups were performed after 1-Way ANOVA followed by post-test: * p <0.05; ** p &lt;0.01; *** p &lt;0.001; **** p <0.0001; ns, not significant.
Figures 17A-17B show Schild analysis of inhibitor peptides. FIG. 17A shows a plot of the concentration of a solid line (a solid line) of 0 nM (colored circle), 0.3 nM (colored rectangle), 1 nM (triangle), 3 nM (inverted triangle), 10 nM (%) As a function of the increasing concentration of IL-23 present in the peptide 993 at the concentration of the peptide 993. The characteristics of the curves are shown in the following graph. Figure 17B shows the same set of experimental results, showing logarithmic scale of Log (volume ratio ^-1 ) as a function of peptide 993 concentration (M). The characteristics of the generated linear function are shown in the following graph. FIG. 17C shows a schematic diagram of an embodiment of the present invention in which the nanoparticles of the present invention have a composition of 0 nM (colored circles), 0.3 nM (colored squares), 1 nM (triangles), 3 nM (inverted triangles), 10 nM (diamonds), 30 nM (%) As a function of the increasing concentration of IL-23 present in the peptide of SEQ ID NO: The characteristics of the curves are shown in the following graph. FIG. 17D shows a schematic diagram of an embodiment of the present invention in which the nanoparticles of the present invention have a composition of 0 nM (colored circle), 0.3 nM (colored rectangle), 1 nM (triangle), 3 nM (inverted triangle), 10 nM (diamonds), 30 nM (%) As a function of the increasing concentration of IL-23 present in the peptide of SEQ ID NO: The characteristics of the curves are shown in the following graph.
Figures 18A-18B show pharmacokinetic data for peptide 1185, an IL-23R peptide inhibitor. Figure 18A shows the concentration of peptide 1185 in serum and in samples taken from the small intestine and colon. Figure 18B shows the amount (% by volume) of peptide 1185 detected in urine and faeces at 24 hours after oral administration.
Figures 19A-19B show pharmacokinetic data for peptide 980, an IL-23R peptide inhibitor. Figure 19A shows the concentration of peptide 980 in serum and in samples collected from the small intestine and colon. Figure 19B shows the amount (volume%) of peptide 980 detected in urine and faeces at 24 hours after oral administration.

Unless otherwise defined herein, the scientific and technical terms used in this application should have the meanings commonly understood by those skilled in the art. In general, the nomenclature and techniques used in connection with chemistry, molecular biology, cell and cancer biology, immunology, microbiology, pharmacology, and protein and nucleic acid chemistry, and techniques described herein are well known in the art and are described in the art It is commonly used.

As used herein, the following terms have the meanings ascribed thereto, unless otherwise stated.

Throughout this specification, the word " comprise ", or " comprises "or" comprises, " for example, refers to an integer (or component) (Or components), or integers (or integers) groups, without departing from the spirit and scope of the invention.

The singular forms "a," " an ", and "the" include plural referents unless the context clearly dictates otherwise.

The word "comprising" is used to mean "including, but not limited to ". The terms "comprising" and "including, but not limited to" are used interchangeably.

The terms "patient," "subject," and "subject" may be used interchangeably and refer to a human or non-human animal. The term includes mammals such as humans, primates, livestock animals (e.g., cows, pigs), pets (e.g., dogs and cats), and rodents (e.g., mice and rats).

As used herein, the term "peptide" refers to a sequence consisting of two or more amino acids joined together extensively by peptide bonds. It should be understood that the term does not imply a polymer of a particular length of amino acid and is not intended to imply or discriminate whether a polypeptide has been produced using recombinant technology, chemical or enzymatic synthesis, or naturally occurring .

As used herein, expressions that include "sequence identity," "percent identity," "homology (%)," or "sequence that is 50% identical to, for example," means that the sequences include nucleotides On a per-nucleotide basis or on an amino acid-to-amino acid basis. Thus, "sequence identity (%)" means that two sequences that are optimally aligned on the comparison window are compared and the same nucleotide base (e.g., A, T, C, G, I) The number of positions at which both sequences are found can be determined by measuring the number of positions found in both sequences Calculating the number of matched positions, dividing the number of matched positions by the total number of positions in the comparison window (i.e., window size), and multiplying the result by 100 to obtain the sequence identity (%) .

The calculation of sequence similarity or sequence identity between sequences (the term is used interchangeably herein) can be performed as follows. To determine the percent identity of two amino acid sequences, or two nucleic acid sequences, the sequences may be aligned for optimal comparison purposes (e.g., for optimal alignment, among the first and second amino acid or nucleic acid sequences Gaps can be introduced in one or both, and non-homologous sequences can be ignored for comparison). In certain embodiments, the length of the aligned reference sequence for comparison is at least 30%, preferably at least 40%, more preferably at least 50%, 60%, and even more preferably at least 70% 80%, 90%, 100%. The amino acid residue or nucleotide is then compared at the corresponding amino acid position or nucleotide position. If the position in the first sequence is occupied by the same amino acid residue or nucleotide as the corresponding position in the second sequence, then the molecule is the same at that position.

The percent identity between two sequences is a function of the number of identical positions shared by the sequence, taking into account the number of gaps that need to be introduced for optimal alignment of the two sequences and the length of each gap.

Sequence comparison between two sequences and determination of identity (%) can be accomplished using a mathematical algorithm. In some embodiments, the percent identity between two amino acid sequences is a Blossum 62 matrix or a PAM250 matrix, and a gap weight of 16, 14, 12, 10, 8, 6, or 4 and a length weight of 1, 2, Needleman and Wunsch (1970, J. Mol. Biol. 48: 444-453), introduced into the GAP program in the GCG software package using 3, 4, 5, &Lt; / RTI &gt; algorithm. In yet another preferred embodiment, the percent identity between the two nucleotide sequences is determined by the NWSgapdna.CMP matrix and the gap weights 40, 50, 60, 70, or 80, and length weights 1, 2, 3, 4, 5, or 6 using the GAP program in the GCG software package. Another exemplary set of parameters includes a blossom 62 scoring matrix that utilizes a gap penalty 12, a gap extension panel 4, and a frame shift gap penalty 5. The percent identity between two amino acid or nucleotide sequences was also calculated using the PAM120 weight residue table, gap length penalty 12, and E. Meyers and W. Can be measured using the algorithm of W. Miller (Literature 1989, Cabios, 4: 11-17).

The peptide sequences described herein may be used, for example, as "query sequences" that perform searches against an open database to identify other family members or related sequences. This search can be performed using the NBLAST and XBLAST programs (version 2.0) of Altschul, et al., (1990, J. Mol. Biol., 215: 403-10). BLAST nucleotide searches can be performed using the NBLAST program, score = 100, wordlength = 12 to obtain nucleotide sequences homologous to the nucleic acid molecules of the invention. BLAST protein searches can be performed using the XBLAST program, score = 50, wordlength = 3 to obtain amino acid sequences homologous to the protein molecules of the invention. To obtain an alignment with a gap for comparison, Gapped BLAST is described in Altschul et al. (Nucleic Acids Res. 25: 3389-3402, 1997). When BLAST and Gapfed BLAST programs are used, default parameters of each program (e.g., XBLAST and NBLAST) may be used.

As used herein, the term "conservative substitution" means that one or more amino acids are replaced by another biologically similar residue. Examples include substitution of amino acid residues with similar characteristics, such as small amino acids, acidic amino acids, polar amino acids, basic amino acids, hydrophobic amino acids and aromatic amino acids. For example, the following table can be referred to. In some embodiments of the invention, one or more of the Met residues is a biological co-precipitate for Met, but in contrast to Met, it is substituted by norleucine (Nle) which is not readily oxidized. Further examples of conservative substitutions by residues not normally found in endogenous, mammalian peptides and proteins include conservative substitutions of Arg or Lys by, for example, ornithine, canavanine, aminoethylcysteine or another basic amino acid . In some embodiments, one or more of the cysteines of the peptide mimetics of the invention may be substituted with another moiety, such as serine. For additional information regarding the silent substitution of the phenotypic mode in peptides and proteins, see, for example, Bowie et al. Science 247, 1306-1310, 1990). In the scheme below, conservative substitutions of amino acids are classified by physicochemical properties. I: neutral, hydrophilic, II: acid and amide, III: basic, IV: hydrophobic, V: aromatic,

In the scheme below, conservative substitutions of amino acids are classified by physicochemical properties. VI: neutral or hydrophobic, VII: acidic, VIII: basic, IX: polar, X: aromatic.

As used herein, the term "amino acid" or "any amino acid" includes any and all naturally occurring amino acids, including naturally occurring amino acids (e.g., a-amino acids), unnatural amino acids, Amino acid. D- and L-amino acids, both. Natural amino acids include those found in nature, such as 23 amino acids that are combined in a peptide chain to form building blocks of various proteins. Although there are some D-amino acids in the bacterial envelope and some antibiotics, they are usually L stereoisomers. The 20 "standard" natural amino acids are listed in the above table. "Non-standard" natural amino acids include pyrolysine (found in methanogenic organisms and other eukaryotes), selenocysteine (present in many eukaryotes as well as in most eukaryotes), and N-formylmethionine , &Lt; / RTI &gt; encoded by the start codon AUG in mitochondria and chloroplasts). An "unnatural" or "non-natural" amino acid is a non-proteinogenic amino acid that is naturally occurring or chemically synthesized (i.e., naturally encoded in a genetic code or not found such). More than 140 kinds of unnatural amino acids are known, and a myriad of combinations are possible. Examples of "unnatural" amino acids include β-amino acids (β ³ and β ² ), homo-amino acids, proline and pyruvic acid derivatives, 3-substituted alanine derivatives, glycine derivatives, ring-substituted phenylalanine and tyrosine derivatives, , Diamino acids, D-amino acids, alpha-methyl amino acids and N-methyl amino acids. Non-natural or non-natural amino acids also include modified amino acids. "Modified" amino acids include amino acids (e.g., natural amino acids) that have been chemically modified to include groups, groups, or chemical moieties that are not naturally present on the amino acid. According to certain embodiments, the peptide inhibitor comprises an intramolecular bond between the two amino acid residues present in the peptide inhibitor. It is understood that the amino acid residues forming the bond can be changed in many cases when they are bonded to each other as compared to when they are not bonded to each other. Reference to a particular amino acid means that it includes the amino acid in its unconjugated and bound state. For example, the amino acid residues homoserine (hSer) or homoserine (Cl) thereof in its unconjugated form can take the form of 2-aminobutyric acid (Abu) when participating in intramolecular linkages according to the present invention. The present invention includes peptide inhibitors that include cross-linking between X4 and X9, as well as peptide inhibitors that do not include cross-linking between X4 and X9 prior to cross-linking formation, for example. Thus, the names hSer and Abu are intended to specify the same amino acid and are used interchangeably.

In most cases, the names of naturally occurring and non-naturally occurring aminoacyl residues used herein are described in Nomenclature of α-amino Acids (Recommendations, 1974), Biochemistry, 14 (2), (1975) The IUPAC Commission and the Biochemical Nomenclature for the Nomenclature of Organic Chemistry as described in the IUPAC-IUB Commission (IUPAC-IUB Commission). Follow. If the names and abbreviations of the amino acid and aminoacyl residue used in this specification and the appended claims are different from the above suggestions, they will be apparent to the reader. Some abbreviations useful for describing the present invention are defined as follows in Table 1a.

[Table 1a]

Throughout this specification, unless the naturally occurring amino acid is referred to as its full name (e.g., alanine, arginine, etc.), the amino acid is specified by its conventional three letter or one letter abbreviation A is alanine, Arg or R is arginine, etc.). Unless otherwise indicated, the three letter or one letter abbreviation of an amino acid refers to the L-isomeric form of the amino acid. As used herein, the term "L-amino acid" refers to the "L" isomeric form of the peptide and, conversely, the term "D-amino acid" refers to the "D" isomeric form of the peptide (D) Asp or D-Asp; Dphe, (D) Phe or D-Phe). Amino acid residues in D-isomeric form may be substituted for any L-amino acid residue, so long as the desired function is maintained by the peptide. When D-amino acids are referred to using a one-letter abbreviation, they can usually be specified in lower case.

In the case of less generic or non-naturally occurring amino acids, a 3 or 4 letter code frequently used for its residues is used, unless it is referred to as its full name (e.g., sarcosine, ornithine, etc.) These include, but are not limited to, Sar or Sarc (sarcosine, i.e. N-methylglycine), Aib (alpha -aminoisobutyric acid), Dab (2,4- diaminobutanoic acid), Dapa (2,3- Glu (? -Glutamic acid), Gaba (? -Aminobutanoic acid),? -Pro (pyrrolidine-3-carboxylic acid), and 8Ado (8-amino-3,6-dioxaoctanoic acid), Abu -Aminobutyric acid),? HPro (? -Homoproline),? HPhe (? -Homophenylalanine) and Bip (?,? Diphenylalanine), and Ida (iminodiacetic acid).

As will be appreciated by those skilled in the art, the peptide sequences disclosed herein are shown to proceed from left to right, with the left end of the sequence being the N-terminus of the peptide and the right end of the sequence being the C-terminus of the peptide. Introducing a "Hy-" moiety to the amino terminus (N-terminus) of the sequence and a "-OH" moiety or "-NH ₂ " moiety to the carboxy terminus (C-terminus) There is a sequence. In this case, and unless otherwise stated, the "Hy-" moiety at the N-terminus of the sequence represents a hydrogen atom corresponding to the presence of a free primary or secondary amino group at the N-terminus, while the C -Terminal " -OH "or" -NH ₂ "moiety represents a hydroxy group or an amino group corresponding to the presence of the C-terminal amido (CONH ₂ ) group, respectively. In each sequence of the present invention, the "-OH" moiety at the C-terminal may be substituted for the "-NH ₂ " moiety at the C-terminal, and vice versa.

As used herein, "DRP" means a disulfide-rich peptide.

As used herein, the term "dimer" broadly refers to a peptide comprising two or more small monomeric subunits. Specific dimers include two DRPs. The dimer of the present invention includes homodimers and heterodimers. The monomeric subunit of the dimer may be linked at its C- or N-terminus, or it may be linked via an internal amino acid residue. Each monomer subunit of the dimer can be linked through the same site, or each can be linked via another site (e.g., C-terminus, N-terminus, or internal site).

As used herein, the term "NH _2" may refer to an free amino present at the amino terminus of a polypeptide. As used herein, the term "OH" may refer to a free carboxyl group present at the carboxy terminus of the peptide. In addition, as used herein, the term "Ac " refers to the acetyl protection through acylation of the C- or N-terminal of the polypeptide. In certain peptides shown herein, NH ₂ is located at the C-terminus of the peptide, which refers to the amino group.

As used herein, the term "carboxy" refers to -CO ₂ H.

As used herein, the term "copper co-implant replacement" refers to any amino acid or other analog moiety that is similar to an amino acid whose chemical and / or structural properties are specified.

As used herein, the term "cyclized" refers to a reaction in which, for example, a portion of a polypeptide is linked to another portion of the polypeptide by a disulfide bridge or other similar bond to form a closed ring.

As used herein, the term "subunit" refers to one of a pair of polypeptide monomers that are linked to form a dimeric peptide composition.

As used herein, the term "linker moiety" refers to a chemical structure that is capable of linking or linking two peptide monomer subunits together extensively for dimer formation.

As used herein, the term "pharmaceutically acceptable salt" refers to a water or oil-soluble, dispersible, and suitable for treating diseases without undue toxicity, irritation and allergic reactions; Exhibit a salt or amphoteric form of the peptide or compound of the invention that is well suited to a reasonable benefit / risk ratio and effective for its intended use. Salts may be prepared during final isolation and purification of the compounds, or separately by reacting the amino group with a suitable acid. Representative acid addition salts include, but are not limited to, acetate, adipate, alginate, citrate, aspartate, benzoate, benzenesulfonate, nisulfate, butyrate, camphorate, camphorsulfonate, digluconate, glycerophosphate, But are not limited to, organic peroxides, such as formic acid, tartaric acid, fumaric acid, tartaric acid, fumaric acid, tartaric acid, fumaric acid, , Methanesulfonate, naphthylenesulfonate, nicotinate, 2-naphthalenesulfonate, oxalate, pamoate, pectinate, persulfate, 3-phenylpropionate, picrate, pivalate, propionate, succinate , Tartrate, trichloroacetate, trifluoroacetate, phosphate, glutamate, bicarbo Sites, para-toluene sulfonate and undecanoate. In addition, the amino groups in the compounds of the present invention include methyl, ethyl, propyl, and butyl chloride, bromide, and iodide; Dimethyl, diethyl, dibutyl, and diamyl sulfates; Decyl, lauryl, myristyl, and stearyl chloride, bromides, and iodides; And quaternized with benzyl and phenethyl bromide. Examples of acids that can be used to form therapeutically acceptable addition salts include inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid and phosphoric acid, and organic acids such as oxalic acid, maleic acid, succinic acid, and citric acid. Pharmaceutically acceptable salts suitably may be, for example, salts selected from acid addition salts and basic salts. Examples of acid addition salts include chloride salts, citrate salts and acetate salts. Examples of basic salts include salts in which a cation is substituted with an alkali metal cation such as a sodium or potassium ion, an alkaline earth metal cation such as calcium or magnesium ion, as well as a substituted ammonium ion such as N (R1) (R2) (R3) R4) + type ions, wherein R1, R2, R3 and R4 independently represent typically hydrogen, hydrogen, optionally substituted C1-6-alkyl or optionally substituted C2-6-alkenyl, &Lt; / RTI &gt; Examples of related C1-6-alkyl groups include methyl, ethyl, 1-propyl and 2-propyl groups. Examples of possible related C2-6-alkenyl groups include ethenyl, 1-propenyl and 2-propenyl. Other examples of pharmaceutically acceptable salts are found in literature (e.g., Remington's Pharmaceutical Sciences, 17th edition, Alfonso R. Gennaro (Ed.), Mark Publishing Company, Easton, Pa., USA, 1985 (Encyclopedia of Pharmaceutical Technology, 3rd edition, James Swarbrick (Ed.), Informa Healthcare USA (Inc.), NY, USA, 2007); Pharm. Sci. 66: 2 (1977). See also Handbook of Pharmaceutical Salts: Properties, Selection, and Use by Stahl and Wermuth (Wiley-VCH, 2002) for a review of suitable salts. Other suitable basic salts are formed from bases that form non-toxic salts. Representative examples include aluminum, arginine, benzathine, calcium, choline, diethylamine, diol amine, glycine, lysine, magnesium, meglumine, olamine, potassium, sodium, tromethamine and zinc salts. Hemic salts of acids and bases may also be formed, such as hematite and hemicalcium salts.

As used herein, "N (alpha) methylation" describes the methylation of alpha amines of amino acids, also commonly referred to as N-methylation.

As used herein, the term "sym-methylation" or "Arg-Me-sym" describes the symmetric methylation of two nitrogens of the guanidine group of arginine. In addition, the term "asymmetylation" or "Arg-Me-asym" describes the methylation of a single nitrogen of the guanidine group of arginine.

As used herein, the term "acylated organic compound" refers to an amino acid or monomer or dimer, such as a carboxyl group used to acylate the N-terminus of a monomer subunit prior to forming a C- Refers to various compounds having an acid functional group. Non-limiting examples of acylated organic compounds include cyclopropylacetic acid, 4-fluorobenzoic acid, 4-fluorophenylacetic acid, 3-phenylpropionic acid, succinic acid, glutaric acid, cyclopentanecarboxylic acid, Trifluoropropionic acid, 3-fluoromethylbutyric acid, and tetrahedra-2H-pyran-4-carboxylic acid.

The term "alkyl" includes straight chain or branched, bicyclic or cyclic, saturated aliphatic hydrocarbons containing 1 to 24 carbon atoms. Representative saturated straight chain alkyls include but are not limited to methyl, ethyl, n -propyl, n -butyl, n -pentyl, n -hexyl and the like, while saturated branched alkyls include isopropyl, sec- Butyl, isobutyl, tert -butyl, isopentyl, and the like. Representative saturated cyclic alkyls include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and the like, while unsaturated cyclic alkyls include, without limitation, cyclopentenyl, cyclohexenyl, and the like.

The term "mammal" refers to any mammalian species, such as a human, mouse, rat, dog, cat, hamster, guinea pig, rabbit, domestic animal, and the like.

As used herein, a "therapeutically effective amount" of a peptide inhibitor of the invention refers to an amount of a therapeutically effective amount of a peptide inhibitor of the invention that treats an IL-23 / IL-23R-related disorder, including, but not limited to, any of the diseases and disorders described herein (E. G., To reduce inflammation associated with IBD). &Lt; / RTI &gt; In certain embodiments, a therapeutically effective amount will achieve the desired benefit / risk ratio that can be applied to any medical treatment.

"Analogs,""Pheanalogs," or "Tyr analogs" of amino acids refer to analogs of the amino acids mentioned. A variety of amino acid analogs, including Phe and Tyr analogs, are known in the art and are available. In certain embodiments, the amino acid analogs, such as Phe analogs or Tyr analogs, comprise 1, 2, 3, 4, or 5 substitutions, respectively, as compared to Phe or Tyr. In certain embodiments, the substitution is in the side chain of the amino acid. In certain embodiments, Phe analogs have the formula Phe (R ² ) wherein R ² is Hy, OH, CH ₃ , CO ₂ H, CONH ₂ , CONH ₂ OCH ₂ CH ₂ NH ₂ , t- Bu, OCH ₂ CH ₂ NH ₂ , phenoxy, OCH ₃ , O allyl, Br, Cl, F, NH ₂ , N ₃ , or guanadino. In certain embodiments, R ² is CONH ₂ OCH ₂ CH ₂ NH ₂ , OCH ₃ , CONH ₂ , OCH _3, or CO ₂ H. Examples of Phe analogs hPhe, Phe (4-OMe) , α-Me-Phe, hPhe (3,4- _{dimethoxy), Phe (4-CONH 2} ), Phe ( 4-fluorophenyl), Phe (4- iguana dino), Phe (4-tBu) , Phe (4-CN), Phe (4-Br), Phe (4-OBzl), Phe (4-NH 2), ΒhPhe (4-F), Phe ( 4-F), Phe (3,5 DiF), Phe (CH 2 CO 2 H), Phe ( penta -F), Phe (3,4-Cl 2), Phe (3,4-F 2), Phe (4-CF _3), ββ- di _{PheAla, Phe (4-N 3} ), Phe [4- ( 2-aminoethoxy)], 4-benzyl _{alanine, Phe (4-CONH 2)} , Phe (3 , _{4-dimethoxy), Phe (4-CF 3} ), Phe (2,3-Cl 2), and including, Phe (2,3-F _2), but it is not limited thereto. Examples of Tyr analogues include, but are not limited to, hTyr, N-Me-Tyr, Tyr (3- t Bu), Tyr (4-N ₃ ) and?

Peptide inhibitors of IL-23R

23 receptor gene (IL-23R) gene and inflammatory bowel disease (IBD) through genome-wide association studies (GWAS), demonstrating that IL-23 signaling is altered Suggesting that perturbation may be related to the pathogenesis of the disease. The present invention provides compositions and methods for modulating the IL-23 pathway through selective antagonism of IL-23R by orally treating with a peptide that is stable and localized in gastrointestinal (GI) tissue. A variety of assays mimicking the various compartments of the GI environment have identified novel inhibitory peptides that are uniquely resistant to oxidation / reduction conditions and proteolytic degradation. Functionally, this peptide strongly neutralizes IL-23-mediated signal transduction in transformed human cell lines and in human primary cells. Peptides do not block the interaction between IL-6 and IL-6R, or they do not antagonize the IL-12 signaling pathway, so the binding of IL-23R is selective. In addition, the orally delivered peptides were found to show a significant reduction in colon weight to length ratio, colonic macroscopic score, neutrophil infiltration, and histological properties comparable to that of the control anti-IL-23p19 mAb As shown, 2,4,6-trinitrobenzenesulfonic acid (TNBS) -induced, is effective in attenuating colitis in a rat model with acute IBD.

The present invention generally relates to peptides having IL-23R antagonist activity, including both peptide monomers and peptide dimers, both. In certain embodiments, the present invention shows a novel paradigm for the treatment of IBD and other diseases and disorders by orally delivering antagonists of IL-23. IBD represents local inflammation of the intestinal tissue; Therefore, beneficial therapeutic agents act from the intestinal lumen of the intestine, resulting in a high drug concentration in the affected tissue, minimizing systemic availability and improving efficacy and safety when compared to the whole body approach. Oral administration of the compounds of the present invention would be effective, safe and continuous delivery for long-term treatment of IBD and other diseases and disorders by maximizing drug levels in the affected intestinal tissues, while limiting drug concentrations in the circulation It is expected.

In certain embodiments, the present invention relates to various peptides, or peptide dimers, including hetero- or homologous monomer subunits, which form a cyclized structure via disulfide or other linkage. In certain embodiments, the disulfide or other bond is an intramolecular bond. The cyclized structures of monomeric monomeric subunits of peptide monomeric inhibitors and peptide dimeric inhibitors have been found to increase the efficacy and selectivity of peptide inhibitors. In certain embodiments, the peptide dimer inhibitor comprises one or more intermolecular bonds linking two monomeric peptide subunits in a peptide dimer inhibitor, such as an intermolecular bridge between two cysteine residues, one at a time in each peptide monomer subunit .

The present invention provides a peptide inhibitor that binds to IL-23R, which may be a monomer or a dimer. In certain embodiments, the peptide inhibitor inhibits the binding of IL-23 to IL-23R. In certain embodiments, IL-23R is human IL-23R and IL-23 is human IL-23. In certain embodiments, a peptide inhibitor of the invention comprises at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70% , At least 80%, or at least 90%. Methods for measuring binding are well known in the art and include ELISA assays as described in the appended examples.

In certain embodiments, a peptide inhibitor of the invention is administered at a concentration of > 1 mM, < 1 mM, < 1 mM, Has an IC50 of from 500 nM to 1000 nM, <500 nM, <250 nM, <100 nM, <50 nM, <25 nM, <10 nM, <5 nM, <2 nM, <1 nM, . Methods for measuring activity are known in the art and include any of those described in the appended examples.

In certain embodiments, the peptide inhibitors of the present invention are characterized by an increase in stimulated intestinal fluid (SIF) or simulated gastric fluid (SGF) and / or under redox conditions (e.g., DTT) as compared to control peptides Increased stability, increased gastrointestinal stability, or increased stability. In certain embodiments, the control peptides are unrelated peptides of the same or similar length. In certain embodiments, the control peptide is a peptide having the same or a highly related amino acid sequence (e. &Gt; 90% sequence identity) as the peptide inhibitor. In certain embodiments, the control peptide has the same or a highly related amino acid sequence (e. G.,> 90% sequence identity) as the peptide inhibitor, but can include, for example, a cyclization via an intramolecular bond between two amino acid residues in the control peptide Or not dimerized, or does not comprise a conjugate for stabilization. In certain embodiments, the only difference between a peptide inhibitor and a control peptide is that the peptide inhibitor comprises one or more amino acid substitutions that introduce one or more amino acid residues into the peptide inhibitor, wherein the introduced amino acid residue (s) And forms an intra-sulfide disulfide or thioether bond with another amino acid. One example of a control for a peptide dimer inhibitor is a monomer having the same sequence as one of the monomer subunits present in the peptide dimer inhibitor. One example of a control for a peptide inhibitor comprising a conjugate is a peptide that has the same sequence but does not include a conjugated moiety. In certain embodiments, the control peptide is a peptide (e. G., A naturally occurring peptide) corresponding to a region of IL-23 that binds to IL-23R.

Methods for determining the stability of peptides are known in the art. In certain embodiments, the stability of the peptide is measured using the SIF assay, for example, as described in Example 3. In certain embodiments, the stability of the peptide is measured using the SGF assay, for example, as described in Example 3. In certain embodiments, the half-life of a peptide inhibitor under a given set of conditions (e.g., temperature) (e.g., SIF or SGF or DTT) is greater than 1 min, greater than 10 min, less than 20 min Greater than 30 minutes, greater than 60 minutes, greater than 90 minutes, greater than 120 minutes, greater than 3 hours, or greater than 4 hours. In certain embodiments, the temperature is about 25 캜, about 4 캜, or about 37 캜, and the pH is physiological pH, or about pH 7.4.

In some embodiments, the half-life is measured in vitro using any suitable method known in the art, e.g., in some embodiments, the stability of the peptides of the invention is determined by incubating pre-warmed human serum (Sigma Sigma). &Lt; / RTI &gt; Typically samples are taken at various time points up to a maximum of 24 hours and the peptides or peptide dimers are separated from serum proteins and analyzed for the stability of the sample by LC-MS using the presence of peptides or peptide dimers of interest Analyze.

In some embodiments, the peptide inhibitors of the present invention exhibit improved solubility or improved aggregation characteristics as compared to control peptides. The solubility can be measured through any suitable method known in the art. In some embodiments, methods suitable for measuring solubility, which are well known in the art, include various buffers (acetate pH 4.0, acetate pH 5.0, phos / citrate pH 5.0, phosphorus citrate pH 6.0, PH 6.0, pH 7.0, pH 7.5, strong PBS pH 7.5, Tris pH 7.5, Tris pH 8.0, glycine pH 9.0, water, acetic acid (pH 5.0) and others known in the art) And testing flocculation or solubility using standard techniques. This includes, for example, visual precipitation methods for detecting surface hydrophobicity and flocculation or fibrillation, dynamic light scattering, circular polarization dichroism, and fluorescent dyes. In some embodiments, improved solubility means that the peptide has greater solubility in the given liquid than the control peptide. In some embodiments, improved aggregation means that the peptide is less aggregated in a given liquid under the given set of conditions than the control peptide.

In certain embodiments, which when delivered orally are beneficial in achieving high compound concentrations in intestinal tissue, the peptide inhibitors of the present invention are stable in the gastrointestinal (GI) environment. Protein-degrading metabolism in the GI tract can be detected by enzymes secreted from the pancreas into the lumen or produced as a brush border enzyme (pepsin, trypsin, chymotrypsin, elastase, aminopeptidase, and carboxypeptidase A / B). Proteases typically cleave peptides and proteins in the extended conformation. In a serous, reducing environment, disulfide bonds can be cleaved, thereby forming linear peptides and rapidly proteolysis. The lumenal oxidation-reduction environment is usually measured by the Cys / CySS redox cycle. In enterocytes, the related activity includes multiple digestive enzymes such as CYP450 and UDP-glucuronosyl-transferase. Finally, bacteria present in the colon in concentrations ranging from 10 ¹⁰ to 10 ¹² CFU / ml constitute another metabolic barrier. In certain embodiments, the peptide inhibitor is tilted from strong acidity (pH 1.5-1.9) above to basic (pH 6-7.5) in the small intestine, followed by a variety of pHs with weak acidity in the colon (pH 5-7) . The peptide inhibitor is stable during the passage through various GI compartments, a process which is estimated to take 3-4 h in the intestine and 6-48 h in the colon.

In some embodiments, the peptide inhibitors of the present invention can be used in combination with other peptide inhibitors such as, for example, less degradation than a control peptide over a period of time, such as less than about 10%, less than about 20% , Or about 40% or less, or about 50% or less (i.e., greater decomposition stability). In some embodiments, degradation stability is measured by any suitable method known in the art. In some embodiments, the degradation is enzymatic degradation. For example, in certain embodiments, the peptide inhibitor has reduced susceptibility to degradation by trypsin, chymotrypsin or elastase. In some embodiments, suitable methods for determining the degradation stability known in the art are described in Hawe et al., J Pharm Sci, Vol. 101, No. 3, 2012, pp. 895-913, which is incorporated herein by reference in its entirety). In some embodiments, the method is used to screen strong peptide sequences that have an increased shelf life. In certain embodiments, peptide stability is measured using SIF or SGF assays as described herein.

In certain embodiments, the peptide inhibitors of the present invention inhibit or reduce IL-23-mediated inflammation. In a related embodiment, a peptide inhibitor of the present invention inhibits or reduces IL-23-mediated secretion of at least one cytokine by, for example, binding to IL-23R on the cell surface and inhibiting binding of IL-23 to the cell. In certain embodiments, the peptide inhibitors of the invention inhibit or reduce the activation of IL-23-mediated Jak2, Tyk2, Stat1, Stat3, Stat4, or Stat5. Methods for measuring cytokine secretion inhibition and signaling molecule inhibition are known in the art. For example, inhibition of IL-23 / IL-23R signaling can be measured by measuring the level of phospho-STAT3 levels in cell lysates, as described in the appended examples, including Example 2. [

In certain embodiments, the peptide inhibitors of the present invention inhibit or reduce IL-23-mediated inflammation. In a related embodiment, a peptide inhibitor of the present invention inhibits or reduces IL-23-mediated secretion of at least one cytokine by, for example, binding to IL-23R on the cell surface and inhibiting binding of IL-23 to the cell. In certain embodiments, the peptide inhibitors of the invention inhibit or reduce the activation of IL-23-mediated Jak2, Tyk2, Stat1, Stat3, Stat4, or Stat5. Methods for measuring cytokine secretion inhibition and signaling molecule inhibition are known in the art. For example, inhibition of IL-23 / IL-23R signaling can be measured by measuring the level of phospho-STAT3 levels in cell lysates, as described in the appended examples, including Example 2. [

In certain embodiments, the peptide inhibitor has increased redox stability compared to the control peptide. Various assays that can be used to measure redox stability are known and are available. Any of these assays can be used to determine the redox stability of the peptide inhibitors of the present invention.

In certain embodiments, the present invention provides various peptide inhibitors that bind to, or associate with, IL-23R in vitro or in vivo to destroy or block binding between IL-23 and IL-23R. In certain embodiments, the peptide inhibitor binds to and / or inhibits human IL-23R. In certain embodiments, the peptide inhibitor binds to and / or inhibits both human and rodent IL-23R. In certain embodiments, the peptide inhibitor binds to and / or inhibits both human and rat IL-23R. In certain embodiments, the peptide inhibitor not only inhibits rat IL-23R by at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 95% Or bind to, or inhibit, human IL-23R. In certain embodiments, the peptide inhibitor binds and / or inhibits preferentially human and / or rat IL-23R compared to murine IL-23R. In certain embodiments, the peptide inhibitor binds preferentially to rat IL-23R as compared to murine IL-23R. In certain embodiments, the peptide inhibitor binds preferentially to human IL-23R as compared to murine IL-23R. In certain embodiments, binding of the peptide inhibitor to murine IL-23R results in less than 75%, less than 50%, less than 40%, less than 30%, or less than 20% of the binding of the same peptide inhibitor to human IL-23R and / or rat IL- %, Or less than 10%. In certain embodiments of a peptide inhibitor that binds to and / or inhibits human IL-23R and / or rat IL-23R preferentially compared to murine IL-23R, the peptide inhibitor is human IL-23R or rat IL- But binds to the region of IL-23R that is destroyed by the presence of additional amino acids present in mouse IL-23R. In one embodiment, the additional amino acid present in mouse IL-23R corresponds to a region corresponding to about amino acid residue 315 to about amino acid residue 340 of the murine IL-23R protein, such as the amino acid region NWQPWSSPFVHQTSQETGKR (see, e.g., Figure 4) Lt; / RTI &gt; In certain embodiments, the peptide inhibitor binds to the region of human IL-23R from about amino acid 230 to about amino acid residue 370.

In certain embodiments, the peptide inhibitor exhibits GI-restricted localization after oral administration. In certain embodiments, greater than 50%, greater than 60%, greater than 70%, greater than 80%, or greater than 90% of the orally administered peptide inhibitors are localized to the gastrointestinal tract organs and tissues. In certain embodiments, the blood plasma level of an orally administered peptide inhibitor is less than 20%, less than 10%, less than 5%, less than 2%, or less than 1% of the level of peptide inhibitor observed in the small intestine mucosa, colon mucosa, % Or 0.5%.

The various peptide inhibitors of the present invention may consist solely of natural amino acids. Alternatively, the peptide inhibitor may include non-natural amino acids including, but not limited to, modified amino acids. In certain embodiments, the modified amino acid comprises a natural amino acid that is chemically modified to include groups, groups, or chemical moieties that are not naturally present on the amino acid. The peptide inhibitor of the present invention may further comprise one or more D-amino acids. Still further, the peptide inhibitors of the present invention may comprise amino acid analogs.

In certain embodiments, the peptide inhibitors of the present invention comprise one or more modified or unnatural amino acids. For example, in certain embodiments, the peptide inhibitor is selected from the group consisting of Dab, Dap, Pen, Sarc, Cit, Cav, hLeu, 2-Nal, D-1-Nal, D- , α-MePhe, α-MeTyr , α-MeTrp, β-hPhe, Phe (4-CF 3), 2-2- indane, indane 1-1-, cyclobutyl, β-hPhe, Gla, Phe (4- NH ₂ ), hPhe, 1-Nal, Nle, homo amino acid, D-amino acid, 4,4'-biphenylalanine (Bip), cyclobutyl- Phe [4- (2- amino-ethoxy)], Phe [4- (2- acetylamino-ethoxy-to)], Phe (4-CONH 2), Phe (4-Me), Tyr (Bzl), or Tyr ( Me), Phe (3,4-diF 2), Phe (3,4-Cl 2), Phe (3-Me), Phe [4- ( 2-aminoethoxy)], Phe [4- (2- in acetylamino-ethoxy)], Phe (Br), Phe (4-CONH 2), Phe (Cl), Phe (4-CN), Phe (4- guar dino), Phe (4-Me) , Phe (4 _{-NH 2), Phe (4-} N3), Tyr, Tyr (Bzl), or Tyr (Me), Phe (3,4- dimethoxy), _{5-hydroxy-Trp, Phe (3,4-Cl 2} ) , Tyr (3-tBu), and various N-methylated amino acids and alpha-methyl amino acids. In some embodiments of the invention, the peptide inhibitor comprises one or more non-natural amino acids as set forth in Table Ia below. It will be understood that various other substitutions of natural amino acids with other modified or unnatural amino acids and with modified or unnatural amino acids may be made thereby achieving similar desired results and such substitutions may be made within the teachings and spirit of the invention It will be understood by those skilled in the art. In certain embodiments, the peptide inhibitor of the present invention is an amino acid sequence or peptide inhibitor structure as set forth in any of the tables, attached sequence listing or attached drawings, wherein the one or more residues are substituted with a modified or non- But are not limited to, any of those described herein.

The present invention also includes any of the peptide inhibitors described herein, either in free form or in salt form. Thus, embodiments of any of the peptide inhibitors described herein (and related methods of use thereof) include a pharmaceutically acceptable salt of a peptide inhibitor.

The present invention is also directed to a compound of the present invention, wherein the one or more L-amino acid residues are substituted with an amino acid residue in the D isomeric form, e.g., wherein L-Ala is replaced by D-Ala, Any of the peptide inhibitors described herein, including, but not limited to, any of those comprising the sequences set forth in any of the above.

In certain embodiments of the peptide inhibitors described herein, the peptide inhibitor comprises one or more non-natural or non-natural amino acid residues.

The present invention includes any of the peptide monomer inhibitors described herein, linked to linker moieties, including any of the specific linker moieties described herein. In certain embodiments, the linker is attached to the N-terminal or C-terminal amino acid, while in other embodiments, the linker is attached to the internal amino acid. In certain embodiments, the linker is attached to an internal amino acid in each of the two internal amino acids, e.g., two monomeric subunits forming a dimer. In some embodiments of the invention, a peptide inhibitor is attached to one or more of the linker moieties presented.

The invention also encompasses peptides and peptide dimers comprising peptides having at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to the peptide sequence of the peptide inhibitors described herein. In certain embodiments, a peptide inhibitor of the invention comprises a core peptide sequence and one or more N-terminal and / or C-terminal modifications (e.g., Ac and NH ₂ ) and / or one or more conjugated linker moieties and / / RTI &gt; and / or half-life extending moieties. As used herein, a core peptide sequence is an amino acid sequence of a peptide without modification or conjugation. For example, the peptide inhibitor: [Palm] - [isoGlu] - [PEG4] - [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2- The key peptide sequence for [Aib] - [Lys (Ac)] - NN-NH ₂ is [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal ] - [Aib] - [Lys (Ac)] - NN.

In certain embodiments, the monomeric subunit of the peptide inhibitor or peptide inhibitor of the invention comprises 7 to 35 amino acid residues, 8 to 35 amino acid residues, 9 to 35 amino acid residues, 10 to 35 amino acid residues, One or more amino acid residues from 7 to 25 amino acid residues, from 8 to 25 amino acid residues, from 9 to 25 amino acid residues, from 10 to 25 amino acid residues, from 7 to 20 amino acid residues, from 8 to 20 amino acid residues, The amino acid sequence of SEQ ID NOs: 1 to 20 amino acid residues, 10 to 20 amino acid residues, 7 to 18 amino acid residues, 8 to 18 amino acid residues, 9 to 18 amino acid residues, or 10 to 18 amino acid residues, Include one or more additional non-amino acid moieties, such as a conjugated chemical moiety, such as a PEG or linker moiety, Or made to him, or made him. In certain embodiments, the peptide inhibitors of the present invention (including, but not limited to, any of the embodiments of SEQ ID X, SEQ ID I, SEQ ID II, SEQ ID III, The monomeric subunit thereof) is greater than 10, greater than 12, greater than 15, greater than 20, greater than 25, greater than 30, or greater than 35 amino acids, such as from 35 to 50 amino acids. In certain embodiments, the peptide inhibitor (or a monomeric subunit thereof) comprises less than 50, less than 35, less than 30, less than 25, less than 20, less than 15, less than 12, Or less than 10 amino acids. In certain embodiments, the monomeric subunits of the peptide inhibitor (or peptide monomer inhibitor) are selected from the group consisting of 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, or 35 amino acid residues. In certain embodiments, the monomeric subunit of the peptide inhibitor of the present invention comprises 10 to 18 amino acid residues and optionally one or more additional non-amino acid moieties, such as a conjugated chemical moiety, such as PEG or linker Or comprises a moiety. In various embodiments, the monomeric subunit comprises 7 to 35 amino acid residues, 7 to 20 amino acid residues, 8 to 20 amino acid residues, 9 to 20 amino acid residues, 10 to 20 amino acid residues, 8 From 8 to 19 amino acid residues, from 8 to 18 amino acid residues, from 9 to 18 amino acid residues, or from 10 to 18 amino acid residues. In certain embodiments of any of the various sequences set forth herein, X is selected from the group consisting of 7 to 35 amino acid residues, 8 to 35 amino acid residues, 9 to 35 amino acid residues, 10 to 35 amino acid residues, One or more amino acid residues from 7 to 25 amino acid residues, from 8 to 25 amino acid residues, from 9 to 25 amino acid residues, from 10 to 25 amino acid residues, from 7 to 18 amino acid residues, from 8 to 18 amino acid residues, To 18 amino acid residues, or from 10 to 18 amino acid residues.

Certain exemplary peptide inhibitors described herein comprise at least 12 amino acid residues. However, the present invention also encompasses peptide inhibitors comprising fragments of any of the peptide sequences described herein, including peptide inhibitors having 7, 8, 9, 10, or 11 amino acid residues. For example, the peptide inhibitor of the present invention may comprise a peptide comprising or consisting of X4-X9, X4-X10, X4-X11, X4-X12, X4-X13, X4-X14, X4- . In certain embodiments, the present invention encompasses any of the formulas, sequences, or tables provided herein, wherein any one or more of X10, X11, X12, X13, X14, X15, But are not limited to, peptides having any of the sequences described herein. In certain embodiments, at least one of X13, X14, X15, or X16 is absent.

In certain embodiments of the invention, the peptide inhibitor, or its X region, is not present in the antibody. In certain embodiments, the peptide inhibitor, or its X region, is not present in the V _H or V _L region of the antibody.

In certain embodiments of the peptide inhibitors described herein, the peptide inhibitor comprises one or more non-natural or non-natural amino acid residues.

In certain embodiments, the peptide inhibitors of the present invention are cyclized via cyclic amide linkages, disulfide linkages, or thioether linkages. In certain embodiments, the binding is an intramolecular bond between two amino acid residues in a peptide inhibitor or monomer subunit thereof.

Peptide inhibitor

A peptide inhibitor of the present invention may be a compound having any of the structures described herein, including a peptide having any of the amino acid sequences described herein, a compound comprising any of the peptide sequences described herein, And a dimer consisting of any of the compounds. Peptide inhibitors of the present invention include, for example, those that do not have a bond between X4 and X9 and that have both, before and after cross-linking, introduced between X4 and X9. Exemplary peptides of the invention include amino acid sequences or structures described in any of the attached tables, examples, figures and sequence listing.

In certain embodiments, the invention includes a peptide inhibitor of an interleukin-23 receptor, or a pharmaceutically acceptable salt or solvate thereof, wherein the peptide inhibitor comprises an amino acid sequence of the following sequence (Xa):

(Xa) X1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12-

In this formula,

X1 is any amino acid, or is absent;

X2 is any amino acid, or is absent;

X3 is any amino acid or is absent;

X4 is any amino acid or chemical moiety capable of forming a bond with X9;

X5 is any amino acid;

X6 is any amino acid;

X7 is any amino acid;

X8 is any amino acid;

X9 is any amino acid or chemical moiety capable of forming a bond with X4;

X10 is any amino acid;

X11 is any amino acid;

X12 is any amino acid;

X13 is any amino acid;

X14 is any amino acid;

X15 is any amino acid,

X16 is any amino acid, or is absent;

X17 is any amino acid or is absent;

X18 is any amino acid or is absent;

X19 is any amino acid, or is absent;

X20 is any amino acid, or is absent,

Here, X4 and X9 may form a bond with each other. In certain embodiments, the bond is a disulfide bond, a thioether bond, a lactam bond, a triazole ring, a selenoether bond, a diselenide bond, or an olefin bond. In certain embodiments, the bond is a disulfide bond or a thioether bond. In certain embodiments, the peptide inhibitor is cyclized via a bond between X4 and X9. In certain embodiments, the peptide inhibitor inhibits the binding of interleukin-23 (IL-23) to the IL-23 receptor. In certain embodiments, when X4 is not an amino acid, X1, X2, and X3 are absent. In certain embodiments, Xl is a D-amino acid or is absent. In certain embodiments, X2 is a D-amino acid or is absent. In certain embodiments, X3 is a D-amino acid or is absent. In certain embodiments, X16 is a D-amino acid or is absent. In certain embodiments, X17 is a D-amino acid, or is absent. In certain embodiments, X18 is a D-amino acid or is absent. In certain embodiments, X19 is a D-amino acid or is absent. In certain embodiments, X20 is a D-amino acid or is absent.

In one embodiment of the peptide inhibitor of SEQ ID NO: Xa,

X1 is absent;

X2 is absent;

X3 is Glu, D-Glu, Arg, (D) Arg, Phe, (D) Phe, 2-Nal, Thr, Leu, (D) Gln;

X4 is Cys, Abu or Pen;

X5 is Ala,? -MeOrn,? -MeSer, Cit, Dap, Dab, Dap (Ac), Gly, Lys, Asn, N-MeGln, N-MeArg, Orn, Gln, Arg, Ser or Thr;

X6 is Asp or Thr;

X7 is Trp or 6-chloro-Trp;

X8 is Glu, Gln or Val;

X9 is Cys, Abu or Pen;

And X10 is 2-Nal, Phe analog of Tyr, Tyr, or analogs, in which, in certain embodiments, X10 is 2-Nal, Phe (3,4- diF 2), Phe (3,4-Cl 2), Phe (3-Me), Phe [ 4- ( 2-aminoethoxy)], Phe [4- (2-acetylamino-ethoxy)], Phe (Br), Phe (4-CONH 2), Phe (Cl) , Phe (4-CN), Phe (4- guar dino), Phe (4-Me) , Phe (4-NH 2), Phe (4-N3), Tyr, Tyr (Bzl), or Tyr (Me) ego;

X11 is 1-Nal, 2-Nal, Phe (3,4- dimethoxy), _{5-hydroxy-Trp, Phe (3,4-Cl 2} ), Trp or Tyr (3-tBu), and;

X12 is selected from the group consisting of 3-Pal, Acpc, Acbc, Acvc, Achc, Agp, Aib,? -Diethyl Gly,? -MeLys,? -MeLys Lys, Octgly, Orn, piperidine, Arg, Ser, Thr or THP;

X13 is selected from the group consisting of Cit, Asp, Dab, Dap, Phe, His, Dap (Peg2-Ac), Dap (pyroglutaric acid), Glu, hArg, Lys, Lys ), Lys (IVA), Lys (Peg4-isoGlu-Palm), Lys (pyroglutaric acid), Lys-succinic acid, Asn, Orn, Gln, Arg, Thr or Val;

X14 is Asp, Dab (Ac), Dap (Ac), Phe, His, Lys (Ac), Met, Asn (isobutyl), Gln, Arg, Tyr or Asp (1,4-diaminobutane);

X15 is Ala, beta Ala, Glu, Gly, Asn, Gln, Arg or Ser;

X16 is any amino acid, or is absent;

X17 is any amino acid or is absent;

X18 is any amino acid or is absent;

X19 is any amino acid, or is absent;

X20 is any amino acid or is absent.

In certain embodiments, X3 is absent. In certain embodiments, X16, X17, X18, X19, and X20 are absent. In certain embodiments, X4 and X9 are Cys, and X4 and X9 are connected through a disulfide bond. In certain embodiments, X4 is Abu, X9 is Pen, and X4 and X9 are connected through a disulfide bond. In certain embodiments, X4 is Abu, X9 is Cys, and X4 and X9 are linked through a thioether linkage.

In another embodiment of the peptide inhibitor of SEQ ID NO: Xa,

X1 is absent;

X2 is absent;

X3 is Glu, D-Glu, Arg, (D) Arg, Phe, (D) Phe, 2-Nal, Thr, Leu, (D) Gln;

X4 is Cys, Abu or Pen;

X5 is Ala,? -MeOrn,? -MeSer, Cit, Dap, Dab, Dap (Ac), Gly, Lys, Asn, Orn, Gln, Arg, Ser or Thr;

X6 is Asp or Thr;

X7 is Trp or 6-chloro-Trp;

X8 is Gln or Val;

X9 is Cys, Abu or Pen;

And X10 is 2-Nal, Phe analog of Tyr, Tyr, or analogs, in which, in certain embodiments, X10 is 2-Nal, Phe (3,4- diF 2), Phe (3-Me), Phe [4- (2-aminoethoxy)], Phe [4- (2-acetylamino-ethoxy)], Phe (Br), Phe (4-CONH 2), Phe (4-Cl), Phe (4-CN), Phe (4- guar dino), Phe (4-Me) , Phe (4-NH 2), Phe (4-N 3), Tyr, Tyr (Bzl), or Tyr (Me), and;

X11 is 1-Nal, 2-Nal, Phe (3,4- dimethoxy), _{5-hydroxy-Trp, Phe (3,4-Cl 2} ), Trp or Tyr (3-tBu), and;

X12 is selected from the group consisting of 3-Pal, Acpc, Acbc, Acvc, Achc, Agp, Aib,? -Diethyl Gly,? -MeLys,? -MeLys , Cav, Cha, Cit, Cpa, D-Asn, His, hLeu, hArg, Lys, Leu, Octgly, Orn, 4-amino-4-carboxy-piperidine, or THP;

X13 is selected from the group consisting of Cit, Asp, Dab, Dap, Phe, His, Dap (Peg2-Ac), Dap (pyroglutaric acid), Glu, hArg, Lys, Lys ), Lys (IVA), Lys (Peg4-isoGlu-Palm), Lys (pyroglutaric acid), Lys-succinic acid, Asn, Orn, Gln, Arg, Thr or Val;

X14 is Dab (Ac), Dap (Ac), Phe, His, Lys (Ac), Met, Asn, Gln, Arg, or Tyr;

X15 is Ala,? Ala, Gly, Asn, Gln, or Ser,

X16 is any amino acid, or is absent;

X17 is any amino acid or is absent;

X18 is any amino acid or is absent;

X19 is any amino acid, or is absent;

X20 is any amino acid or is absent.

In some embodiments, X3 is absent. In certain embodiments, X16, X17, X18, X19, and X20 are absent. In certain embodiments, X4 and X9 are Cys, and X4 and X9 are connected through a disulfide bond. In certain embodiments, X4 is Abu, X9 is Pen, and X4 and X9 are linked through a thioether linkage. In certain embodiments, X4 is Abu, X9 is Cys, and X4 and X9 are linked through a thioether linkage.

In another embodiment of the peptide inhibitor of SEQ ID NO: Xa,

X1 is absent;

X2 is absent;

X3 is Glu, D-Glu, Arg, (D) Arg, Phe, (D) Phe, 2-Nal, Thr, Leu, (D) Gln;

X4 is Cys, Abu or Pen;

X5 is Dap, Dap (Ac), Gly, Lys, Gln, Arg, Ser, Thr or Asn;

X6 is Thr;

X7 is Trp or 6-chloro-Trp;

X8 is Gln;

X9 is Cys, Abu or Pen;

X10 is 2-Nal, a Phe analog, a Tyr, or a Tyr analog, wherein in certain embodiments, X10 is selected from the group consisting of 2-Nal, Phe (3-Me), Phe [4- (2-aminoethoxy) [4- (2-acetylamino-ethoxy)], Phe (4-CONH 2), Phe (4-Me), Phe (4-NH 2), Tyr, Tyr (Bzl), or Tyr (Me), and;

X11 is 1-Nal, 2-Nal, Phe (3,4- _{dimethoxy), Phe (3,4-Cl 2} ), or Trp;

X12 is at least one selected from the group consisting of Acpc, Acbc, Acvc, Achc, Aib, alpha -Diethyl Gly, alpha-MeLys, alpha-MeLys (Ac), alpha-MeLeu, alpha-MeOrn, alpha-MeSer, , Lys, Leu, Arg or THP;

Lys (Ac), Lys (benzoic acid), Lys (glutaric acid), Lys (IVA), Lys , Lys (Peg4-isoGlu-Palm), Lys (pyroglutaric acid), Lys (succinic acid), Asn, Orn, Gln, Arg, or Val;

X14 is Dab (Ac), Dap (Ac), His, Lys (Ac), Asn, Gln, or Tyr;

X15 is Ala, beta Ala, Gly, Asn, Gln, or Ser,

X16 is any amino acid, or is absent;

X17 is any amino acid or is absent;

X18 is any amino acid or is absent;

X19 is any amino acid, or is absent;

X20 is any amino acid or is absent.

In some embodiments, X3 is absent. In certain embodiments, X16, X17, X18, X19, and X20 are absent. In certain embodiments, X4 and X9 are Cys, and X4 and X9 are connected through a disulfide bond. In certain embodiments, X4 is Abu, X9 is Pen, and X4 and X9 are linked through a thioether linkage. In certain embodiments, X4 is Abu, X9 is Cys, and X4 and X9 are linked through a thioether linkage.

In another embodiment of the peptide inhibitor of SEQ ID NO: Xa,

X1 is absent;

X2 is absent;

X3 is Glu, D-Glu, Arg, (D) Arg, Phe, (D) Phe, 2-Nal, Thr, Leu, (D) Gln;

X4 is Cys, Abu or Pen;

X5 is Dap, Dap (Ac), Gln, Ser, Thr or Asn;

X6 is Thr;

X7 is Trp;

X8 is Gln;

X9 is Cys, Abu or Pen;

X10 is a Phe analog, Tyr, or Tyr analog, wherein in certain embodiments, X10 is selected from the group consisting of Phe [4- (2-aminoethoxy)], Phe [4- (2-acetylaminoethoxy) 4-CONH ₂ ), Phe (4-Me), Tyr, Tyr (Bzl), or Tyr (Me);

X11 is 2-Nal or Trp;

X12 is selected from the group consisting of Acpc, Acbc, Acvc, Achc, Aib,? -Diethyl Gly,? -MeLys,? -MeLys (Ac),? -MeLeu,? -MeOrn,? -MeSer,? -MeVal, hLeu, THP;

X13 is Cit, Asp, Glu, Lys, Lys (Ac), Asn, or Gln;

X14 is Dab (Ac), Asn, or His;

X15 is Ala, beta Ala, Gly, Asn, or Gln;

X16 is any amino acid, or is absent;

X17 is any amino acid or is absent;

X18 is any amino acid or is absent;

X19 is any amino acid, or is absent;

X20 is any amino acid or is absent.

In some embodiments, X3 is absent. In certain embodiments, X16, X17, X18, X19, and X20 are absent. In certain embodiments, X4 and X9 are Cys, and X4 and X9 are connected through a disulfide bond. In certain embodiments, X4 is Abu, X9 is Pen, and X4 and X9 are linked through a thioether linkage. In certain embodiments, X4 is Abu, X9 is Cys, and X4 and X9 are linked through a thioether linkage.

In certain embodiments, the peptide inhibitor comprises an amino acid sequence as described in any of the various sequence formulas described herein, for example, Ia-It, IIa-IId, IIIa-IIIe, or IV.

In certain embodiments, the invention includes a peptide inhibitor of an interleukin-23 receptor having the structure of formula (I), or a pharmaceutically acceptable salt or solvate thereof:

R ¹ -XR ² (I)

In this formula,

R ¹ includes a bond, hydrogen, C ¹ -C 6 alkyl, C 6 -C 12 aryl, C 6 -C 12 aryl C 1 -C 6 alkyl, C 1 -C 20 alkanoyl, and the PEGylated version of any of the foregoing, alone or as a spacer thereof ;

R ² is a bond, OH or NH ₂ ;

X is an amino acid comprising an amino acid sequence, such as 7 to 35 amino acid residues. In certain embodiments, R ² is OH or NH ₂ .

In certain embodiments, X comprises a sequence of the sequence formula Xa.

In certain embodiments of the sequence formula (I), X comprises the sequence of the sequence SEQ ID &lt; RTI ID = 0.0 &gt;

(Ia) wherein X1-X2-X3-X4-X5-X6-W-X8-X9-X10-X11-X12-

In this formula,

X1 is any amino acid, or is absent;

X2 is any amino acid, or is absent;

X3 is any amino acid or is absent;

X4 is selected from the group consisting of Cys, Pen, hCys, D-Pen, D-Cys, D-hCys, Met, Glu, Asp, Lys, Orn, Dap, Dab, D-Dap, D- 3-chloro-butyric acid, 3-chloro-isobutyric acid, Abu, beta -D-Lys, Sec, 2-allyl glycine, 2- (3'-butenyl) glycine, 2- (4'-pentenyl) glycine, 2- (5'-hexenyl) glycine, or is absent;

X5 is selected from the group consisting of Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, D-Ala, D-Arg, D-Glu, D-Phe, D- -MeOrn,? -MeSer, CitDap, Dab, Dap (Ac), Gly, Lys, Asn, N-Me-

X6 is Asp, Thr, Asn, Phe, D-Asp, D-Thr, D-Asn, or D-Phe;

X8 is Val, Gln, Glu, or Lys;

D-Dab, D-Dab, D-Asp, D-Glu, D-Lys, Asp, Leu, Val, Phe, Ser, Sec, Abu,? -Azido-Ala-OH, propargylglycine, 2-2-allylglycine, 2- (3'- -Pentenyl) glycine, or 2- (5'-hexenyl) glycine;

X10 is Tyr, Phe, Phe (3,4- F 2), Phe (3,4-Cl 2), F (3-Me), Phe [4- ( 2-aminoethoxy)], Phe [4- (2- (acetyl-amino-ethoxy)], Phe (4-Br ), Phe (4-CONH 2), Phe (4-Cl), Phe (4-CN), Phe (4- guanidino), Phe (4-Me), Phe (4-NH 2), Phe (4-N 3), Phe (4-OMe), Phe (4-OBzl) or Tyr;

X11 is Trp, 1-Nal, 2- Nal, Phe (3,4-OMe 2) 5- hydroxy _{-Trp, Phe (3,4-Cl 2} ) or Tyr (3-t-Bu), and;

X12 is selected from the group consisting of His, Phe, Arg, N-Me-His or Val, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t- ? -MeLys (Ac),? -Me-Leu,? -MeOrn,? -MeSer,? -MeVal, Cha, Cit, Cpa, (D) Asn, Glu, hArg, or Lys;

X13 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, Val,? HAla, Aib, Lys (Ac), Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, Orn or Gln;

X14 is Phe, Tyr? HPhe, Asn, Arg, Qln, Lys (Ac), His; Dap (Ac), Dab (Ac), or Asp;

X15 is GIy, Ser, Thr, Gln, Ala, Sarc, beta -Ala, GIu, Arg or Asn;

X16 is any amino acid, or is absent;

X17 is any amino acid or is absent;

X18 is any amino acid or is absent;

X19 is any amino acid, or is absent;

X20 is any amino acid or is absent.

In certain embodiments of Ia: X5 is selected from the group consisting of Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, D-Ala, D-Arg, D-Glu, D- , D-Ser, D-Aib or D-Sarc; X10 is Tyr or Phe; X11 is Trp, 1-Nal or 2-Nal; X12 is His, Phe, Arg, N-Me-His or Val, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t-butyl-Ala or t-butyl-Gly; X13 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, Val,? HAla, or Aib; X14 is Phe, Tyr or? HPhe; X15 is GIy, Ser, Thr, Gln, Ala or Sarc; X16 is Asp, Glu, Ala, AEA, AEP,? HAla, Gaba, or is absent; X17 is Leu, Lys, Arg, or is absent.

In certain embodiments, X4 is present.

In certain embodiments, the peptide inhibitor is cyclized.

In certain embodiments, the peptide inhibitor is linear or non-pecylated.

In certain embodiments, the peptide inhibitor is cyclized or comprises an intramolecular bond between X4 and X9.

In certain embodiments of formula I, X comprises the sequence of formula Ib:

X1-X2-X3-X4-X5-X6-W-X8-X9-X10-X11-X12-X13-X14-

In this formula,

X1 is any amino acid, or is absent;

X2 is any amino acid, or is absent;

X3 is any amino acid or is absent;

D-Dab, D-Asp, D-Glu, D-Gln, Lys, Sec, 2-chloromethylbenzoic acid, methapto-propionic acid, methapto-butyric acid, 2-chloro-acetic acid, 3-chloropropionic acid, 4-chloro-butyric acid, 3-chloro-isobutyric acid, Abu, (3'-butenyl) glycine, 2- (3'-butenyl) glycine, 2-2-allyl glycine, 2- 2- (5'-hexenyl) glycine, or is absent;

X5 is selected from the group consisting of Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, D-Ala, D-Arg, D-Glu, D- MeOrn,? -MeSer, CitDap, Dab, Dap (Ac), Gly, Lys, Asn, N-Me-Gln, N-Me-Arg, Orn or Gln;

X6 is Asp, Thr, Asn, Phe, D-Asp, D-Thr, D-Asn, or D-Phe;

X8 is Val, Gln, Glu, or Lys;

D-Dab, D-Dab, D-Asp, D-Glu, D-Lys, (3'-butenyl) glycine, 2- (4'-pentenyl) glycine, or 2- (4'-pentenyl) glycine, asparagine, 5'-hexenyl) glycine;

X10 is Tyr, Phe, Phe (3,4- F 2), Phe (3,4-Cl 2), F (3-Me), Phe [4- ( 2-aminoethoxy)], Phe [4- (2- (acetyl-amino-ethoxy)], Phe (4-Br ), Phe (4-CONH 2), Phe (4-Cl), Phe (4-CN), Phe (4- guanidino), Phe (4-Me), Phe (4-NH 2), Phe (4-N 3), Phe (4-OMe), Phe (4-OBzl) or Tyr;

X11 is Trp, 1-Nal, 2- Nal, Phe (3,4-OMe 2) 5- hydroxy _{-Trp, Phe (3,4-Cl 2} ), Tyr (3-t-Bu) , and;

X12 is selected from the group consisting of His, Phe, Arg, N-Me-His, Val, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t- Me-Leu,? -MeOrn,? -MeSer,? -MeVal, Cha, Pyr, Acc Acpc, Acbc, Acvc, Agp, Aib,? -Diethyl Gly,? -MeLys,? -MeLys Cit, Cpa, (D) Asn, Glu, hArg, or Lys;

X13 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, Val,? HAlaAib, Lys (Ac), Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, Orn or Gln;

X14 is Phe, Tyr, or? HPhe, Asn, Arg, Qln, Lys (Ac), His; Dap (Ac), Dab (Ac), or Asp;

X15 is Gly, Ser, Thr, Gln, Ala, or Sarc, [beta] -Ala, Glu, Arg or Asn;

X16 is any amino acid, or is absent;

X17 is any amino acid or is absent;

X18 is any amino acid or is absent;

X19 is any amino acid, or is absent;

X20 is any amino acid or is absent.

In certain embodiments of Ib: X5 is selected from the group consisting of Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, D-Ala, D-Arg, D-Glu, D- , D-Ser, D-Aib or D-Sarc; X10 is Tyr or Phe; X11 is Trp, 1-Nal or 2-Nal; X12 is His, Phe, Arg, N-Me-His, Val, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t-butyl-Ala or t-butyl-Gly; X13 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, Val,? HAla or Aib; X14 is Phe, Tyr or? HPhe; X15 is GIy, Ser, Thr, Gln, Ala, or Sarc; X16 is Asp, Glu, Ala, AEA, AEP,? HAla, Gaba, or is absent; X17 is Leu, Lys, Arg, or is absent.

In certain embodiments, X4 is present.

In certain embodiments, the peptide inhibitor is cyclized.

In certain embodiments, the peptide inhibitor is linear or non-pecylated.

In certain embodiments, the peptide inhibitor is cyclized or comprises an intramolecular bond between X4 and X9.

In certain embodiments of formula I, X comprises the sequence of formula &lt; RTI ID = 0.0 &gt; Ic &

X1-X2-X3-X4-X5-X6-W-X8-X9-Y-X11-X12-X13-X14-

In this formula,

X1 is any amino acid, or is absent;

X2 is any amino acid, or is absent;

X3 is any amino acid or is absent;

X4 is selected from the group consisting of Cys, Pen, hCys, D-Pen, D-Cys, D-hCys, Met, Glu, Asp, Lys, Orn, Dap, Dab, D-Dap, D- 3-chloro-butyric acid, 3-chloro-isobutyric acid, Abu, beta -D-Lys, Sec, 2-allyl glycine, 2- (3'-butenyl) glycine, 2- (4'-pentenyl) glycine, 2- (5'- hexenyl) glycine or , Or absent;

X5 is selected from the group consisting of Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, D-Ala, D-Arg, D-Glu, D- MeOrn,? -MeSer, CitDap, Dab, Dap (Ac), Gly, Lys, Asn, N-Me-Gln, N-Me-Arg, Orn or Gln;

X6 is Asp, Thr, Asn, Phe, D-Asp, D-Thr, D-Asn, or D-Phe;

X8 is Val, Gln, Glu, or Lys;

D-Dab, D-Dab, D-Asp, D-Glu, D-Lys, (3'-butenyl) glycine, 2- (4'-pentenyl) glycine, or 2- (4'-pentenyl) glycine, asparagine, 5'-hexenyl) glycine;

X11 is Trp, 1-Nal, 2- Nal Phe (3,4-OMe 2) 5- hydroxy _{-Trp, Phe (3,4-Cl 2} ) or Tyr (3-t-Bu), and;

X12 is selected from the group consisting of His, Phe, Arg, N-Me-His, Val, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t- ? -MeLys (Ac),? -Me-Leu,? -MeOrn,? -MeOrn, ? -MeSer,? -MeVal, Cha, Cit, Cpa, (D) Asn, Glu, hArg, or Lys;

Lys (Ac), Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, Orn, or Gln;

X14 is Phe, Tyr,? HPhe, Asn, Arg, Qln, Lys (Ac), His; Dap (Ac), Dab (Ac), or Asp;

X15 is GIy, Ser, Thr, Gln, Ala, Sarc, beta -Ala, GIu, Arg or Asn;

X16 is any amino acid, or is absent;

X17 is any amino acid or is absent;

X18 is any amino acid or is absent;

X19 is any amino acid, or is absent;

X20 is any amino acid or is absent.

In certain embodiments of Ic, X5 is selected from the group consisting of Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, D-Ala, D-Arg, D-Glu, D- , D-Ser, D-Aib, or D-Sarc; X11 is Trp, 1-Nal, or 2-Nal; X12 is His, Phe, Arg, N-Me-His, Val, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t-butyl-Ala or t-butyl-Gly; X13 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, Val,? HAla, or Aib; X14 is Phe, Tyr, or? HPhe; X15 is GIy, Ser, Thr, Gln, Ala, or Sarc; X16 is Asp, Glu, Ala, AEA, AEP,? HAla, Gaba, or is absent; X17 is Leu, Lys, Arg, or is absent.

In certain embodiments, X4 is present.

In certain embodiments, the peptide inhibitor is cyclized.

In certain embodiments, the peptide inhibitor is linear or non-pecylated.

In certain embodiments, the peptide inhibitor is cyclized or comprises an intramolecular bond between X4 and X9.

In certain embodiments of SEQ ID &lt; RTI ID = 0.0 &gt; I, &lt; / RTI &gt; X comprises the sequence of the following sequence Id:

X1-X2-X3-C-X5-X6-W-X8-C-X10-X11-X12-X13-X14-

In this formula,

X1 is any amino acid, or is absent;

X2 is any amino acid, or is absent;

X3 is any amino acid or is absent;

X5 is selected from the group consisting of Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, D-Ala, D-Arg, D-Glu, D- MeOrn,? -MeSer, CitDap, Dab, Dap (Ac), Gly, Lys, Asn, N-Me-Gln, N-Me-Arg, Orn or Gln;

X6 is Asp, Thr, Asn, Phe, D-Asp, D-Thr, D-Asn, or D-Phe;

X8 is Val, Gln, Glu, or Lys;

X10 is Tyr Phe, Phe (3,4-F 2), Phe (3,4-Cl 2), F (3-Me), Phe [4- ( 2-aminoethoxy)], Phe [4- ( 2- (acetyl-amino-ethoxy)], Phe (4-Br ), Phe (4-CONH 2), Phe (4-Cl), Phe (4-CN), Phe (4- guanidino), Phe (4-Me), Phe ( 4-NH 2), Phe (4-N 3), Phe (4-OMe), Phe (4-OBzl) or Tyr;

X11 is Trp, 1-Nal, 2- Nal, Phe (3,4-OMe 2) 5- hydroxy _{-Trp, Phe (3,4-Cl 2} ), Tyr (3-t-Bu) , and;

X12 is selected from the group consisting of His, Phe, Arg, N-Me-His, Val, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t- ? -MeLys (Ac),? -Me-Leu,? -MeOrn,? -MeSer,? -MeVal, Cha, Cit, Cpa, (D) Asn, Glu, hArg, or Lys;

X13 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, Val,? HAla, Aib, Lys (Ac), Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, Orn or Gln;

X14 is Phe, Tyr,? HPhe, Asn, Arg, Qln, Lys (Ac), His, Dap (Ac), Dab (Ac) or Asp;

X15 is GIy, Ser, Thr, Gln, Ala, Sarc, beta -Ala, GIu, Arg or Asn;

X16 is any amino acid, or is absent;

X17 is any amino acid or is absent;

X18 is any amino acid or is absent;

X19 is any amino acid, or is absent;

X20 is any amino acid, or is absent,

Where X4 and X9 are optionally connected by an intramolecular disulfide bridge.

In certain embodiments of Id: X5 is selected from the group consisting of Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, D-Ala, D-Arg, D-Glu, D- , D-Ser, D-Aib, or D-Sarc; X10 is Tyr or Phe; X11 is Trp, 1-Nal, or 2-Nal; X12 is His, Phe, Arg, N-Me-His, Val, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t-butyl-Ala or t-butyl-Gly; X13 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, Val,? HAla, or Aib; X14 is Phe, Tyr, or? HPhe; X15 is GIy, Ser, Thr, Gln, Ala, or Sarc; X16 is Asp, Glu, Ala, AEA, AEP,? HAla, Gaba, or is absent; X17 is Leu, Lys, Arg, or is absent.

In certain embodiments of formula I, X comprises the sequence of formula &lt; RTI ID = 0.0 &gt; Ie &

X1-X2-X3-X4-X5-X6-W-X8-X9-X10-X11-X12-X13-X14-

In this formula,

X1 is any amino acid, or is absent;

X2 is any amino acid, or is absent;

X3 is any amino acid or is absent;

X4 is Pen, hCys, D-Pen, D-Cys, or D-hCys;

X5 is selected from the group consisting of Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, D-Ala, D-Arg, D-Glu, D- MeOrn,? -MeSer, CitDap, Dab, Dap (Ac), Gly, Lys, Asn, N-Me-Gln, N-Me-Arg, Orn or Gln;

X6 is Asp, Thr, Asn, Phe, D-Asp, D-Thr, D-Asn, or D-Phe;

X8 is Val, Gln, Glu, or Lys;

X9 is Pen, hCys, D-Pen, D-Cys, D-hCys;

X10 is Tyr, Phe Phe (3,4-F 2), Phe (3,4-Cl 2), F (3-Me), Phe [4- ( 2-aminoethoxy)], Phe [4- ( 2- (acetyl-amino-ethoxy)], Phe (4-Br ), Phe (4-CONH 2), Phe (4-Cl), Phe (4-CN), Phe (4- guanidino), Phe (4-Me), Phe ( 4-NH 2), Phe (4-N 3), Phe (4-OMe), Phe (4-OBzl) or Tyr;

X11 is Trp, 1-Nal, 2- Nal, Phe (3,4-OMe 2) 5- hydroxy _{-Trp, Phe (3,4-Cl 2} ) or Tyr (3-t-Bu), and;

X12 is selected from the group consisting of His, Phe, Arg, N-Me-His, Val, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t- ? -MeLys (Ac),? -Me-Leu,? -MeOrn,? -MeSer,? -MeVal, Cha, Cit, Cpa, (D) Asn, Glu, hArg, or Lys;

X13 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, Val,? HAla, Aib, Lys (Ac), Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, Orn or Gln;

X14 is Phe, Tyr,? HPhe, Asn, Arg, Qln, Lys (Ac), His; Dap (Ac), Dab (Ac), or Asp;

X15 is GIy, Ser, Thr, Gln, Ala, Sarc, beta -Ala, GIu, Arg or Asn;

X16 is any amino acid, or is absent;

X17 is any amino acid or is absent;

X18 is any amino acid or is absent;

X19 is any amino acid, or is absent;

X20 is any amino acid, or is absent,

Where X4 and X9 are optionally connected by an intramolecular disulfide bridge.

In certain embodiments of Ie X5 is selected from the group consisting of Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, D-Ala, D-Arg, D-Glu, D- , D-Ser, D-Aib, or D-Sarc; X10 is Tyr or Phe; X11 is Trp, 1-Nal, or 2-Nal; X12 is His, Phe, Arg, N-Me-His, Val, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t-butyl-Ala or t-butyl-Gly; X13 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, Val,? HAla, or Aib; X14 is Phe, Tyr, or? HPhe; X15 is GIy, Ser, Thr, Gln, Ala, or Sarc; X16 is Asp, Glu, Ala, AEA, AEP,? HAla, Gaba, or is absent; X17 is Leu, Lys, Arg, or is absent.

In certain embodiments, X4 is present.

In certain embodiments, the peptide inhibitor is cyclized.

In certain embodiments, the peptide inhibitor is linear or non-pecylated.

In certain embodiments, the peptide inhibitor is cyclized or comprises an intramolecular bond between X4 and X9.

In certain embodiments, X4 and X9 and both are Pen.

In certain embodiments of formula I, X comprises the sequence of the following sequence formula If: &lt; RTI ID = 0.0 &gt;

When X1-X2-X3-X4-X5-X6-W-X8-X9-X10-X11-X12-X13-

In this formula,

X1 is any amino acid, or is absent;

X2 is any amino acid, or is absent;

X3 is any amino acid or is absent;

X4 is Glu, Lys, Orn, Dap, Dab, D-Dap, D-Dab, D-Asp, D-Glu, D-Lys or Asp;

X5 is selected from the group consisting of Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, D-Ala, D-Arg, D-Glu, D- MeOrn,? -MeSer, Cit, Dap, Dab, Dap (Ac), Gly, Lys, Asn, N-Me-Gln, N-Me-Arg, Orn or Gln;

X6 is Asp, Thr, Asn, Phe, D-Asp, D-Thr, D-Asn, or D-Phe;

X8 is Val, Gln, Glu, or Lys;

X9 is Glu, Lys, Orn, Dap, Dab, D-Dap, D-Dab, D-Asp, D-Glu, D-Lys or Asp;

X10 is selected from the group consisting of Tyr, Phe, Phe (3,4-F2), Phe (3,4-Cl2) Phe (4-CON), Phe (4-CN), Phe (4-guanidino), Phe (4-Br), Phe -Me), Phe (4-NH2 ), Phe (4-N 3), Phe (4-OMe), Phe (4-OBzl) or Tyr;

X11 is Trp, 1-Nal, 2- Nal, Phe (3,4-OMe 2) 5- hydroxy _{-Trp, Phe (3,4-Cl 2} ) or Tyr (3-t-Bu), and;

X12 is selected from the group consisting of His, Phe, Arg, N-Me-His, Val, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t- -MeLys (Ac),? -Me-Leu,? -MeOrn,? -MeSer,? -MeVal , Cha, Cit, Cpa, (D) Asn, Glu, hArg, or Lys;

X13 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, Val,? HAla, Aib, Lys (Ac), Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, Orn or Gln;

X14 is Phe, Tyr,? HPhe, Asn, Arg, Qln, Lys (Ac), His; Dap (Ac), Dab (Ac), or Asp;

X15 is GIy, Ser, Thr, Gln, Ala, Sarc, beta -Ala, GIu, Arg or Asn;

X16 is any amino acid, or is absent;

X17 is any amino acid or is absent;

X18 is any amino acid or is absent;

X19 is any amino acid, or is absent;

X20 is any amino acid, or is absent,

Wherein X4 and X9 are optionally cyclized via an intramolecular bond.

In certain embodiments of If: X5 is selected from the group consisting of Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, D-Ala, D-Arg, D-Glu, D- , D-Ser, D-Aib, or D-Sarc; X6 is Asp, Thr, Asn, Phe, D-Asp, D-Thr, D-Asn, or D-Phe; X8 is Val, Gln, Glu, or Lys; X9 is Glu, Lys, Orn, Dap, Dab, D-Dap, D-Dab, D-Asp, D-Glu, D-Lys or Asp; X10 is Tyr or Phe; X11 is Trp, 1-Nal, or 2-Nal; X12 is His, Phe, Arg, N-Me-His, Val, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t-butyl-Ala or t-butyl-Gly; X13 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, Val,? HAla, or Aib; X14 is Phe, Tyr, or? HPhe; X15 is GIy, Ser, Thr, Gln, Ala, or Sarc; X16 is Asp, Glu, Ala, AEA, AEP,? HAla, Gaba, or is absent; X17 is Leu, Lys, Arg, or is absent.

In certain embodiments, the intramolecular bond is a lactam bond.

In certain embodiments of formula I, X comprises the sequence of the following sequence formula Ig:

X1-X16-X17-X18-X19-X20 (Ig) X1-X2-X3-X4-X5-X6-W-X8-

In this formula,

X1 is any amino acid, or is absent;

X2 is any amino acid, or is absent;

X3 is any amino acid or is absent;

X4 is? -Azido-Ala-OH, or propargylglycine;

X5 is selected from the group consisting of Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, D-Ala, D-Arg, D-Glu, D- MeOrn,? -MeSer, Cit, Dap, Dab, Dap (Ac), Gly, Lys, Asn, N-MeGln, N-MeArg, Orn or Gln;

X6 is Asp, Thr, Asn, Phe, D-Asp, D-Thr, D-Asn, or D-Phe;

X8 is Val, Gln, Glu, or Lys;

X9 is? -Azido-Ala-OH or propargylglycine;

X10 is Tyr, Phe, Phe (3,4- F 2), Phe (3,4-Cl 2), F (3-Me), Phe [4- ( 2-aminoethoxy)], Phe [4- (2- (acetyl-amino-ethoxy)], Phe (4-Br ), Phe (4-CONH 2), Phe (4-Cl), Phe (4-CN), Phe (4- guanidino), Phe (4-Me), Phe (4-NH 2), Phe (4-N 3), Phe (4-OMe), Phe (4-OBzl) or Tyr;

X11 is Trp, 1-Nal, 2- Nal, Phe (3,4-OMe 2) 5- hydroxy _{-Trp, Phe (3,4-Cl 2} ) or Tyr (3-t-Bu), and;

X12 is selected from the group consisting of His, Phe, Arg, N-Me-His, Val, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t- -MeLys (Ac),? -Me-Leu,? -MeOrn,? -MeSer,? -MeVal , Cha, Cit, Cpa, (D) Asn, Glu, hArg, or Lys;

X13 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, Val,? HAla, Aib, Lys (Ac), Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, Orn or Gln;

X14 is Phe, Tyr,? HPhe, Asn, Arg, Qln, Lys (Ac), His; Dap (Ac), Dab (Ac), or Asp;

X15 is Gly, Ser, Thr, Gln, Ala, or Sarc, [beta] -Ala, Glu, Arg or Asn;

X16 is any amino acid, or is absent;

X17 is any amino acid or is absent;

X18 is any amino acid or is absent;

X19 is any amino acid, or is absent;

X20 is any amino acid, or is absent,

Where X4 and X9 are optionally cyclized via an intramolecular triazole ring.

In certain embodiments of Ig: X5 is selected from the group consisting of Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, D-Ala, D-Arg, D-Glu, D- , D-Ser, D-Aib, or D-Sarc; X6 is Asp, Thr, Asn, Phe, D-Asp, D-Thr, D-Asn, or D-Phe; X8 is Val, Gln, Glu, or Lys; X9 is? -Azido-Ala-OH or propargylglycine; X10 is Tyr or Phe; X11 is Trp, 1-Nal, or 2-Nal; X12 is His, Phe, Arg, N-Me-His, Val, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t-butyl-Ala or t-butyl-Gly; X13 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, Val,? HAla, or Aib; X14 is Phe, Tyr, or? HPhe; X15 is GIy, Ser, Thr, Gln, Ala, or Sarc; X16 is Asp, Glu, Ala, AEA, AEP,? HAla, Gaba, or is absent; X17 is Leu, Lys, Arg, or is absent.

In certain embodiments of formula I, X comprises the sequence of formula &lt; RTI ID = 0.0 &gt; Ih &

X1-X2-X3-C-X5-X6-W-X8-C-Y-X11-H-X13-F-X15-

In this formula,

X1 is any amino acid, or is absent;

X2 is any amino acid, or is absent;

X3 is any amino acid or is absent;

X4 is 2-allyl glycine, 2- (3'-butenyl) glycine, 2- (4'-pentenyl) glycine, or 2- (5'-hexenyl) glycine;

X5 is Ala, Arg, Sarc,? -MeOrn,? -MeSer, Cit, Dap, Dab, Dap (Ac), Gly, Lys, Asn, N-MeGln, N-MeArg, Orn or Gln;

X6 is Asp, Thr, or Asn;

X8 is Val, Gln, or GIu;

X9 is 2-allyl glycine, 2- (3'-butenyl) glycine, 2- (4'-pentenyl) glycine, or 2- (5'-hexenyl) glycine;

X11 is Trp, 1-Nal, 2- Nal, Phe (3,4-OMe 2) 5- hydroxy _{-Trp, Phe (3,4-Cl 2} ) or Tyr (3-t-Bu), and;

X13 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys,? HAla, Val, Aib, Lys (Ac), Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, Orn or Gln;

X15 is GIy, Ser, Thr, Gln, Ala, Sarc, beta -Ala, GIu, Arg or Asn;

X16 is any amino acid, or is absent;

X17 is any amino acid or is absent;

X18 is any amino acid or is absent;

X19 is any amino acid, or is absent;

X20 is any amino acid, or is absent,

Wherein X4 and X9 are optionally cyclized through an intramolecular ring closing methasis to yield the corresponding olefin.

In certain embodiments of Ih: X5 is Ala, Arg, or Sarc; X6 is Asp, Thr, or Asn; X11 is Trp, 1-Nal, or 2-Nal; X13 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys,? HAla, Val, or Aib; X15 is GIy, Ser, Thr, Gln, Ala, or Sarc; X16 is Asp, Glu, Ala, AEA, AEP,? HAla, Gaba, or is absent; X17 is Leu, Lys, Arg, or is absent.

In certain embodiments of formula I, X comprises the sequence of formula &lt; RTI ID = 0.0 &gt;

X1-X2-X3-X4-X5-X6-W-X8-X9-X10-X11-X12-X13-X14-

In this formula,

X1 is any amino acid, or is absent;

X2 is any amino acid, or is absent;

X3 is any amino acid or is absent;

X4 is selected from the group consisting of Cys, Pen, hCys, D-Pen, D-Cys, D-hCys, 2- chloromethylbenzoic acid, methapto-propionic acid, methapto-butyric acid, 2- Chloro-butyric acid, or 3-chloro-isobutyric acid;

X5 is selected from the group consisting of Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, D-Ala, D-Arg, D-Glu, D- Aib or D-Sarc,? -MeOrn,? -MeSer, Cit, Dap, Dab, Dap (Ac), Gly, Lys, Asn, N-MeGln, N-MeArg, Orn or Gln;

X6 is Asp, Thr, Asn, Phe, D-Asp, D-Thr, D-Asn, or D-Phe;

X8 is Val, Gln, Glu, or Lys;

X9 is Cys, Pen, hCys, D-Pen, D-Cys, D-hCys, or Abu;

X10 is Tyr, Phe, Phe (3,4- F 2), Phe (3,4-Cl 2), F (3-Me), Phe [4- ( 2-aminoethoxy)], Phe [4- (2- (acetyl-amino-ethoxy)], Phe (4-Br ), Phe (4-CONH 2), Phe (4-Cl), Phe (4-CN), Phe (4- guanidino), Phe (4-Me), Phe (4-NH 2), Phe (4-N 3), Phe (4-OMe), Phe (4-OBzl) or Tyr;

X11 is Trp, 1-Nal, 2- Nal, Phe (3,4-OMe 2) 5- hydroxy _{-Trp, Phe (3,4-Cl 2} ) or Tyr (3-t-Bu), and;

X12 is selected from the group consisting of His, Phe, Arg, N-Me-His, Val, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t- ? -MeLys (Ac),? -Me-Leu,? -MeOrn,? -MeSer,? -MeVal, Cha, Cit, Cpa, (D) Asn, Glu, hArg, or Lys;

X13 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, Val,? HAla, Aib, Lys (Ac), Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, Orn or Gln;

X14 is Phe, Tyr,? HPhe, Asn, Arg, Qln, Lys (Ac), His; Dap (Ac), Dab (Ac), or Asp;

X15 is GIy, Ser, Thr, Gln, Ala, Sarc, beta -Ala, GIu, Arg or Asn;

X16 is any amino acid, or is absent;

X17 is any amino acid or is absent;

X18 is any amino acid or is absent;

X19 is any amino acid, or is absent;

X20 is any amino acid, or is absent,

Where X4 and X9 are optionally cyclized via an intramolecular thioether linkage.

D-Phe, D-Leu, D-Thr, D-Thr, , D-Ser, D-Aib, or D-Sarc; X6 is Asp, Thr, Asn, Phe, D-Asp, D-Thr, D-Asn, or D-Phe; X10 is Tyr or Phe; X11 is Trp, 1-Nal, or 2-Nal; X12 is His, Phe, Arg, N-Me-His, Val, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t-butyl-Ala or t-butyl-Gly; X13 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, Val,? HAla, or Aib; X14 is Phe, Tyr, or? HPhe; X15 is GIy, Ser, Thr, Gln, Ala, or Sarc; X16 is Asp, Glu, Ala, AEA, AEP,? HAla, Gaba, or is absent; X17 is Leu, Lys, Arg, or is absent.

In certain embodiments of formula I, X comprises the sequence of formula &lt; RTI ID = 0.0 &gt; Ij &

(X1-X2-X3-X4-X5-X6-W-X8-X9-X10-X11-X12-X13-X14-

In this formula,

X1 is any amino acid, or is absent;

X2 is any amino acid, or is absent;

X3 is any amino acid or is absent;

X4 is Sec, 2-chloromethylbenzoic acid, 3-chloro-propionic acid, 4-chloro-butyric acid, 3-chloro-isobutyric acid, or Abu;

X5 is selected from the group consisting of Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, D-Ala, D-Arg, D-Glu, D- MeOrn,? -MeSer, Cit, Dap, Dab, Dap (Ac), Gly, Lys, Asn, N-MeGln, N-MeArg, Orn or Gln;

X6 is Asp, Thr, Asn, Phe, D-Asp, D-Thr, D-Asn, or D-Phe;

X8 is Val, Gln, Glu, or Lys;

X9 is Sec or Abu;

X10 is Tyr, Phe, Phe (3,4- F 2), Phe (3,4-Cl 2), F (3-Me), Phe [4- ( 2-aminoethoxy)], Phe [4- (2-aminoethoxy), Phe [4- (2- (acetyl-amino-ethoxy)], Phe (4-Br ), Phe (4-CONH 2), Phe (4-Cl), Phe (4- CN), Phe (4- guanidino), Phe (4-Me) , Phe (4-NH 2), Phe (4-N 3), Phe (4-OMe), Phe (4-OBzl) or Tyr ego;

X11 is Trp, 1-Nal, 2- Nal, Phe (3,4-OMe 2) 5- hydroxy _{-Trp, Phe (3,4-Cl 2} ) or Tyr (3-t-Bu), and;

X12 is selected from the group consisting of His, Phe, Arg, N-Me-His, Val, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t- ? -MeLys (Ac),? -Me-Leu,? -MeOrn,? -MeSer,? -MeVal, Cha , Cit, Cpa, (D) Asn, Glu, hArg, or Lys;

X13 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, Val,? HAla, Aib, Lys (Ac), Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, Orn or Gln;

X14 is Phe, Tyr,? HPhe, Asn, Arg, Qln, Lys (Ac), His; Dap (Ac), Dab (Ac), or Asp;

X15 is GIy, Ser, Thr, Gln, Ala, Sarc, beta -Ala, GIu, Arg or Asn;

X16 is any amino acid, or is absent;

X17 is any amino acid or is absent;

X18 is any amino acid or is absent;

X19 is any amino acid, or is absent;

X20 is any amino acid, or is absent,

Wherein X4 and X9 are optionally cyclized via intramolecular thioseleno or diselenide linkages.

In certain embodiments of Ij: X5 is selected from the group consisting of Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, D-Ala, D-Arg, D-Glu, D- , D-Ser, D-Aib, or D-Sarc; X10 is Tyr or Phe; X11 is Trp, 1-Nal, or 2-Nal; X12 is His, Phe, Arg, N-Me-His, Val, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t-butyl-Ala or t-butyl-Gly; X13 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, Val,? HAla, or Aib; X14 is Phe, Tyr, or? HPhe; X15 is GIy, Ser, Thr, Gln, Ala, or Sarc; X16 is Asp, Glu, Ala, AEA, AEP,? HAla, Gaba, or is absent; X17 is Leu, Lys, Arg, or is absent.

In certain embodiments of formula I, X comprises the sequence of formula Ik:

X1-X2-X3-X4-X5-X6-W-X8-X9-X10-X11-X12-X13-X14-

In this formula,

X1 is any amino acid, or is absent;

X2 is any amino acid, or is absent;

X3 is any amino acid or is absent;

X4 is selected from the group consisting of Cys, Pen, hCys, D-Pen, D-Cys, D-hCys, Met, Glu, Asp, Lys, Orn, Dap, Dab, D-Dap, D- D-Lys, or is absent;

X5 is selected from the group consisting of Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, D-Ala, D-Arg, D-Glu, D- MeOrn,? -MeSer, Cit, Dap, Dab, Dap (Ac), Gly, Lys, Asn, N-MeGln, N-MeArg, Orn or Gln;

X6 is Asp, Thr, Asn, Phe, D-Asp, D-Thr, D-Asn, or D-Phe;

X8 is Val, Gln, Glu, or Lys;

D-Dab, D-Dab, D-Asp, D-Glu, D-Lys, Asp, Leu, Val, Phe, or Ser;

X10 is Tyr, Phe, Phe (3,4- F 2), Phe (3,4-Cl 2), F (3-Me), Phe [4- ( 2-aminoethoxy)], Phe [4- (2- (acetyl-amino-ethoxy)], Phe (4-Br ), Phe (4-CONH 2), Phe (4-Cl), Phe (4-CN), Phe (4- guanidino), Phe (4-Me), Phe (4-NH 2), Phe (4-N 3), Phe (4-OMe), Phe (4-OBzl) or Tyr;

X11 is Trp, 1-Nal, 2- Nal, Phe (3,4-OMe 2) 5- hydroxy _{-Trp, Phe (3,4-Cl 2} ) or Tyr (3-t-Bu), and;

X12 is selected from the group consisting of His, Phe, Arg, N-Me-His, Val, D-His, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t- ? -MeLys (Ac),? -Me-Leu,? -MeOrn,? -MeSer,? -MeLe2, ? -MeVal, Cha, Cit, Cpa, (D) Asn, Glu, hArg, or Lys;

X13 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, Val,? HAla, Aib, Lys (Ac), Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, Orn or Gln;

X14 is Phe, Tyr,? HPhe, Asn, Arg, Qln, Lys (Ac), His; Dap (Ac), Dab (Ac) or Asp, or absent;

X15 is GIy, Ser, Thr, Gln, Ala, Sarc, beta -Ala, GIu, Arg or Asn or is absent;

X16 is any amino acid, or is absent;

X17 is any amino acid or is absent;

X18 is any amino acid or is absent;

X19 is any amino acid, or is absent;

X20 is any amino acid or is absent.

D-Phe, D-Leu, D-Thr, D-Thr, , D-Ser, D-Aib, or D-Sarc; X10 is Tyr or Phe; X11 is Trp, 1-Nal, or 2-Nal; X12 is His, Phe, Arg, N-Me-His, Val, D-His, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t-butyl-Ala or t-butyl-Gly; X13 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, Val,? HAla, Aib, or is absent; X14 is Phe, Tyr,? HPhe, or is absent; X15 is Gly, Ser, Thr, Gln, Ala, Sarc, or is absent; X16 is Asp, Glu, Ala, AEA, AEP,? HAla, Gaba, Leu, or is absent; X17 is Leu, Lys, Arg, or is absent.

In certain embodiments of formula I, X comprises or consists of a sequence of the following sequence Il:

(XII), X1-X2-X3-X4-X5-X6-W-X8-X9-X10-X11-X12-X13-X14-

In this formula,

X1 is any amino acid, or is absent;

X2 is any amino acid, or is absent;

X3 is any amino acid or is absent;

X4 is selected from the group consisting of Cys, Pen, hCys, D-Pen, D-Cys, D-hCys, Met, Glu, Asp, Lys, Orn, Dap, Dab, D-Dap, D- D-Lys, or is absent;

X5 is selected from the group consisting of Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, α-MeOrn, α- MeSer, Cit, Dap, Dab, Dap Ac, Gly, Lys, Asn, -MeArg, Orn or Gln;

X6 is Asp, Thr, Asn, or Phe;

X8 is Val, Gln, Glu, or Lys;

D-Dab, D-Dab, D-Asp, D-Glu, D-Lys, Asp, Leu, Val, Phe, or Ser;

X10 is Tyr, Phe, Phe (3,4- F 2), Phe (3,4-Cl 2), F (3-Me), Phe [4- ( 2-aminoethoxy)], Phe [4- (2- (acetyl-amino-ethoxy)], Phe (4-Br ), Phe (4-CONH 2), Phe (4-Cl), Phe (4-CN), Phe (4- guanidino), Phe (4-Me), Phe (4-NH 2), Phe (4-N 3), Phe (4-OMe), Phe (4-OBzl) or Tyr;

X11 is Trp, 1-Nal, 2- Nal ,, Phe (3,4-OMe 2) 5- hydroxy _{-Trp, Phe (3,4-Cl 2} ) or Tyr (3-t-Bu), and;

X12 is selected from the group consisting of His, Phe, Arg, N-Me-His, Val, D-His, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t- ? -MeLys (Ac),? -Me-Leu,? -MeOrn,? -MeSer,? -MeLe2, ? -MeVal, Cha, Cit, Cpa, (D) Asn, Glu, hArg, or Lys;

X13 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, Val,? HAla, Aib, Lys (Ac), Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, Orn, Does not exist;

X14 is Phe, Tyr,? HPhe, Asn, Arg, Qln, Lys (Ac), His; Dap (Ac), Dab (Ac) or Asp, or absent;

X15 is GIy, Ser, Thr, Gln, Ala, Sarc, beta -Ala, GIu, Arg or Asn or is absent;

X16 is any amino acid, or is absent;

X17 is any amino acid or is absent;

X18 is any amino acid or is absent;

X19 is any amino acid, or is absent;

X20 is any amino acid or is absent.

In certain embodiments of Il: X5 is Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, or Sarc; X10 is Tyr or Phe; X11 is Trp, 1-Nal, or 2-Nal; X12 is His, Phe, Arg, N-Me-His, Val, D-His, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t-butyl-Ala or t-butyl-Gly; X13 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, Val,? HAla, Aib, or is absent; X14 is Phe, Tyr,? HPhe, or is absent; X15 is Gly, Ser, Thr, Gln, Ala, Sarc, or is absent; X16 is Asp, Glu, Ala, AEA, AEP,? HAla, Gaba, Leu, or is absent; X17 is Leu, Lys, Arg, or is absent.

In certain embodiments, Xl 3 is selected from the group consisting of Thr, Sarc, Glu, Phe, Arg, Leu, Lys,? HAla, Aib, Lys (Ac), Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, to be. In certain embodiments, X13 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, beta hAla, or Aib.

In certain embodiments, X 14 is Phe, Tyr,? HPhe, Asn, Arg, Qln, Lys (Ac), His; Dap (Ac), Dab (Ac), or Asp. In certain embodiments, X14 is Phe, Tyr, or? HPhe.

In certain embodiments, Xl 5 is GIy, Ser, Thr, Gln, Ala, Sarc, beta -Ala, GIu, Arg or Asn. In certain embodiments, X15 is GIy, Ser, Thr, Gln, Ala, or Sarc.

In certain embodiments, X 12 is selected from the group consisting of alpha amino acids such as 4-amino-4-carboxy-tetrahydropyran, Achc Acpc, Acbc, Aib, a-MeGly (diethyl) ? -Me-Leu,? -MeOrn,? -MeSer,? -MeVal.

In certain embodiments, X13 is present.

In certain embodiments, X13 and X14 are present.

In certain embodiments, X13, X14, and X15 are present.

In certain embodiments, X4 is present.

In certain embodiments, the peptide inhibitor is cyclized.

In certain embodiments, the peptide inhibitor is linear or non-pecylated.

In certain embodiments, the peptide inhibitor is cyclized or comprises an intramolecular bond between X4 and X9.

In certain embodiments of the peptide inhibitor of SEQ ID &lt; RTI ID = 0.0 &gt; I, &lt; / RTI &gt; X comprises or consists of the sequence of the following sequence Im:

(I m), X 1-X 2 -X 3 -X 4 -X 5 -X 6 -W-X 8 -X 9 -Y-X 11 -X 12 -X 13 -X 14 -X 15 -X 16-

In this formula,

X1 is any amino acid, or is absent;

X2 is any amino acid, or is absent;

X3 is any amino acid or is absent;

X4 is selected from the group consisting of Cys, Pen, hCys, D-Pen, D-Cys, D-hCys, Met, Glu, Asp, Lys, Orn, Dap, Dab, D-Dap, D- D-Lys, or is absent;

X5 is selected from the group consisting of Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, α-MeOrn, α- MeSer, Cit, Dap, Dab, Dap Ac, Gly, Lys, Asn, -MeArg, Orn, or Gln;

X6 is Asp, Thr, Asn, or Phe;

X8 is Val, Gln, Glu, or Lys;

D-Dab, D-Dab, D-Asp, D-Glu, D-Lys, Asp, Leu, Val, Phe, or Ser;

X11 is Trp, 1-Nal, 2- Nal, Phe (3,4-OMe 2); _{5-hydroxy--Trp, Phe (3,4-Cl 2} ), or Tyr (3-t-Bu), and;

X12 is selected from the group consisting of His, Phe, Arg, N-Me-His, Val, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t- -MeLys (Ac),? -Me-Leu,? -MeOrn,? -MeSer,? -MeVal , Cha, Cit, Cpa, (D) Asn, Glu, hArg, or Lys;

X13 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys,? HAla, Val, Aib, Lys (Ac), Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, Orn, Does not exist;

X14 is Phe, Tyr,? HPhe, Asn, Arg, Qln, Lys (Ac), His; Dap (Ac), Dab (Ac), or Asp, or absent;

X15 is GIy, Ser, Thr, Gln, Ala, Sarc, beta -Ala, GIu, Arg or Asn or is absent;

X16 is any amino acid, or is absent;

X17 is any amino acid or is absent;

X18 is any amino acid or is absent;

X19 is any amino acid, or is absent;

X20 is any amino acid or is absent.

In certain embodiments of Im: X5 is Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, or Sarc; X11 is Trp, 1-Nal, or 2-Nal; X12 is His, Phe, Arg, N-Me-His, Val, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t-butyl-Ala or t-butyl-Gly; X13 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys,? HAla, Val, Aib or is absent; X14 is Phe, Tyr,? HPhe, or is absent; X15 is Gly, Ser, Thr, Gln, Ala, Sarc, or is absent; X16 is Asp, Glu, Ala, AEA, AEP,? HAla, Gaba, or is absent; X17 is Leu, Lys, Arg, or is absent.

In certain embodiments, X13 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, beta hAla, or Aib. In certain embodiments, Xl 3 is selected from the group consisting of Thr, Sarc, Glu, Phe, Arg, Leu, Lys,? HAla, Aib, Lys (Ac), Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, to be.

In certain embodiments, X 14 is Phe, Tyr,? HPhe, Asn, Arg, Qln, Lys (Ac), His; Dap (Ac), Dab (Ac), or Asp. In certain embodiments, X14 is Phe, Tyr, or? HPhe.

In certain embodiments, X15 is Gly, Ser, Thr, Gln, Ala, or Sarc, beta -Ala, Glu, Arg or Asn. In certain embodiments, X15 is GIy, Ser, Thr, Gln, Ala, or Sarc.

In certain embodiments, X 12 is selected from the group consisting of alpha amino acids such as 4-amino-4-carboxy-tetrahydropyran, Achc Acpc, Acbc, Aib, a-MeGly (diethyl) ? -Me-Leu,? -MeOrn,? -MeSer,? -MeVal.

In certain embodiments, X13 is present.

In certain embodiments, X13 and X14 are present.

In certain embodiments, X13, X14, and X15 are present.

In certain embodiments, X4 is present.

In certain embodiments, the peptide inhibitor is cyclized.

In certain embodiments, the peptide inhibitor is linear or non-pecylated.

In certain embodiments, the peptide inhibitor is cyclized or comprises an intramolecular bond between X4 and X9.

In certain embodiments of the peptide inhibitor of SEQ ID &lt; RTI ID = 0.0 &gt; I, &lt; / RTI &gt; X comprises or consists of a sequence of the following sequence In:

(In), X1-X2-X3-C-X5-X6-W-X8-C-X10-X11-X12-X13-

In this formula,

X1 is any amino acid, or is absent;

X2 is any amino acid, or is absent;

X3 is any amino acid or is absent;

X5 is selected from the group consisting of Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, α-MeOrn, α- MeSer, Cit, Dap, Dab, Dap Ac, Gly, Lys, Asn, -MeArg, Orn or Gln;

X6 is Asp, Thr, Asn, or Phe;

X8 is Val, Gln, Glu, or Lys;

X10 is Tyr Phe, Phe (3,4-F 2), Phe (3,4-Cl 2), F (3-Me), Phe [4- ( 2-aminoethoxy)], Phe [4- ( 2- (acetyl-amino-ethoxy)], Phe (4-Br ), Phe (4-CONH 2), Phe (4-Cl), Phe (4-CN), Phe (4- guanidino), Phe (4-Me), Phe ( 4-NH 2), Phe (4-N 3), Phe (4-OMe), Phe (4-OBzl) or Tyr;

X11 is Trp, 1-Nal, 2- Nal, Phe (3,4-OMe 2) 5- hydroxy _{-Trp, Phe (3,4-Cl 2} ) or Tyr (3-t-Bu), and;

X12 is selected from the group consisting of His, Phe, Arg, N-Me-His, Val, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t- -MeLys (Ac),? -Me-Leu,? -MeOrn,? -MeSer,? -MeVal , Cha, Cit, Cpa, (D) Asn, Glu, hArg, or Lys;

X13 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys,? HAla, Val, Aib, Lys (Ac), Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, Orn, Does not exist;

X14 is Phe, Tyr,? HPhe, Asn, Arg, Qln, Lys (Ac), His; Dap (Ac), Dab (Ac) or Asp, or absent;

X15 is GIy, Ser, Thr, Gln, Ala, Sarc, beta -Ala, GIu, Arg or Asn or is absent;

X16 is any amino acid, or is absent;

X17 is any amino acid or is absent;

X18 is any amino acid or is absent;

X19 is any amino acid, or is absent;

X20 is any amino acid, or is absent,

Here, Cys at position X4 and Cys at position X9 are optionally connected by a disulfide bridge.

In certain embodiments of In: X5 is selected from the group consisting of Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, alpha-MeOrn, alpha-MeSer, Cit, Dap, Dab, Ac Asn, N-MeGln, N-MeArg, Orn or Gln; X10 is Tyr, Phe, Phe (3,4- F 2), Phe (3,4-Cl 2), F (3-Me), Phe [4- ( 2-aminoethoxy)], Phe [4- (2- (acetyl-amino-ethoxy)], Phe (4-Br ), Phe (4-CONH 2), Phe (4-Cl), Phe (4-CN), Phe (4- guanidino), Phe (4-Me), Phe (4-NH 2), Phe (4-N 3), Phe (4-OMe), Phe (4-OBzl) or Tyr; X11 is Trp, 1-Nal, 2- Nhe, Phe (3,4-OMe ₂ ) 5-hydroxy-Trp, Phe (3,4-Cl ₂ ) or Tyr Ala, or t-butyl-Gly, 4-amino-4-carboxy-tetrahydropyran, Achc Acpc, Acbc, Acvc, Me, Ag, Aib,? -Diethyl Gly,? -MeLys,? -MeLys (Ac),? -Me-Leu,? -MeOrn,? -MeSer,? -MeVal, Cha, Cit, Cpa, Glu, hArg, or Lys; X13 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys,? HAla, Val, Aib, Lys (Ac), Cit, Asp, Dab, Dap, Glu, hArg, (Ac), Dab (Ac), or Asp, or not present, or is absent. ; X15 Glu, Ser, Thr, Gln, Ala, Sarc,? -Ala, Glu, Arg or Asn or not present; X16 is Asp, Glu, Ala, AEA, AEP,? HAla, Gaba, Leu, Lys, Arg, or is absent.

In certain embodiments, Xl 3 is selected from the group consisting of Thr, Sarc, Glu, Phe, Arg, Leu, Lys,? HAla, Aib, Lys (Ac), Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, to be. In certain embodiments, X13 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, beta hAla, or Aib.

In certain embodiments, X 14 is Phe, Tyr,? HPhe, Asn, Arg, Qln, Lys (Ac), His; Dap (Ac), Dab (Ac), or Asp. In certain embodiments, X14 is Phe, Tyr, or? HPhe.

In certain embodiments, Xl 5 is GIy, Ser, Thr, Gln, Ala, Sarc, beta -Ala, GIu, Arg or Asn. In certain embodiments, X15 is GIy, Ser, Thr, Gln, Ala, or Sarc.

In certain embodiments, X 12 is selected from the group consisting of alpha amino acids such as 4-amino-4-carboxy-tetrahydropyran, Achc Acpc, Acbc, Acvc, Aib, ? -Me-Leu,? -MeOrn,? -MeSer,? -MeVal.

In certain embodiments, X13 is present.

In certain embodiments, X13 and X14 are present.

In certain embodiments, X13, X14, and X15 are present.

In certain embodiments of the peptide inhibitors of SEQ ID &lt; RTI ID = 0.0 &gt; I, &lt; / RTI &gt; X comprises or consists of the sequence of the following sequence Io:

X1-X2-X3-C-X5-X6-W-X8-C-Y-X11-H-X13-X14-X15-

In this formula,

X1 is any amino acid, or is absent;

X2 is any amino acid, or is absent;

X3 is any amino acid or is absent;

X5 is selected from the group consisting of Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, α-MeOrn, α- MeSer, Cit, Dap, Dab, Dap Ac, Gly, Lys, Asn, -MeArg, Orn or Gln;

X6 is Asp, Thr, Asn, or Phe;

X8 is Val, Gln, Glu, or Lys;

X11 is Trp, 1-Nal, 2- Nal, Phe (3,4-OMe 2) 5- hydroxy _{-Trp, Phe (3,4-Cl 2} ) or Tyr (3-t-Bu), and;

X13 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys,? HAla, Val, Aib, Lys (Ac), Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, Orn, Does not exist;

X14 is Phe, Tyr, Asn, Arg, Qln, Lys (Ac), His; Dap (Ac), Dab (Ac) or Asp, or absent;

X15 is GIy, Ser, Thr, Gln, Ala, Sarc, beta -Ala, GIu, Arg or Asn or is absent;

X16 is any amino acid, or is absent;

X17 is any amino acid or is absent;

X18 is any amino acid or is absent;

X19 is any amino acid, or is absent;

X20 is any amino acid, or is absent,

Here, Cys at position X4 and Cys at position X9 are optionally connected by a disulfide bridge.

In certain embodiments of Io: X5 is selected from the group consisting of Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, alpha-MeOrn, alpha-MeSer, Cit, Dap, Dab, Asn, N-MeGln, N-MeArg, Orn or Gln; X11 is Trp, 1-Nal, 2- Nal, Phe (3,4-OMe 2), 5- hydroxy _{-Trp, Phe (3,4-Cl 2} ) or Tyr (3-t-Bu), and; X13 is either Thr, Sarc, Glu, Phe, Arg, Leu, Lys,? HAla, Val, Aib, Lys (Ac), Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, Orn, Gln, without doing; X14 is Phe, Tyr, Asn, Arg, Qln, Lys (Ac), His; Dap (Ac), Dab (Ac) Asp, or absent; X15 is GIy, Ser, Thr, Gln, Ala, Sarc, beta -Ala, GIu, Arg or Asn or is absent; X16 is Asp, Glu, Glu, Ala, AEA, AEP,? HAla, Gaba, or is absent; X17 is Leu, Lys, Arg, or is absent.

In certain embodiments, X 12 is selected from the group consisting of alpha amino acids such as 4-amino-4-carboxy-tetrahydropyran, Achc Acpc, Acbc, Acvc, Aib, ? -Me-Leu,? -MeOrn,? -MeSer,? -MeVal.

In certain embodiments, Xl 3 is selected from the group consisting of Thr, Sarc, Glu, Phe, Arg, Leu, Lys,? HAla, Aib, Lys (Ac), Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, . In certain embodiments, X13 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, beta hAla or Aib.

In certain embodiments, X14 is selected from the group consisting of Phe, Tyr, Asn, Arg, Qln, Lys (Ac), His; Dap (Ac), Dab (Ac), or Asp. In certain embodiments, X14 is Phe or Tyr.

In certain embodiments, Xl 5 is GIy, Ser, Thr, Gln, Ala, Sarc, beta -Ala, GIu, Arg or Asn. In certain embodiments, X15 is GIy, Ser, Thr, Gln, Ala or Sarc.

In certain embodiments, X13 is present.

In certain embodiments, X13 and X14 are present.

In certain embodiments, X13, X14, and X15 are present.

In certain embodiments of the peptide inhibitor of SEQ ID &lt; RTI ID = 0.0 &gt; I, &lt; / RTI &gt; X comprises or consists of a sequence of the following sequence Ip:

X1-X2-X3-C-X5-X6-W-X8-C-Y-X11-H-X13-F-X15-

In this formula,

X1 is any amino acid, or is absent;

X2 is any amino acid, or is absent;

X3 is any amino acid or is absent;

X5 is Ala, Arg, Sarc,? -MeOrn,? -MeSer, Cit, Dap, Dab, Dap (Ac), Gly, Lys, Asn, N-MeGln, N-MeArg, Orn or Gln;

X6 is Asp, Thr, or Asn;

X8 is Val, Gln, or GIu;

X11 is Trp, 1-Nal, 2- Nal, Phe (3,4-OMe 2) 5- hydroxy _{-Trp, Phe (3,4-Cl 2} ) or Tyr (3-t-Bu), and;

X13 is either Thr, Sarc, Glu, Phe, Arg, Leu, Lys,? HAla, Val, Aib, Lys (Ac), Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, Orn, Gln, without doing;

X15 is Gly, Ser, Thr, Gln, Ala, Sarc,? -Ala, Glu, Arg Asn or is absent;

X16 is any amino acid, or is absent;

X17 is any amino acid or is absent;

X18 is any amino acid or is absent;

X19 is any amino acid, or is absent;

X20 is any amino acid, or is absent,

Here, Cys at position X4 and Cys at position X9 are optionally connected by a disulfide bridge.

In certain embodiments of Ip, X5 is Ala, Arg, or Sarc; X11 is Trp, 1-Nal, or 2-Nal; X13 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys,? HAla, Val, Aib or is absent; X15 is Gly, Ser, Thr, Gln, Ala, Sarc, or is absent; X16 is Asp, Glu, Ala, AEA, AEP,? HAla, Gaba, or is absent; X17 is Leu, Lys, Arg, or is absent.

In certain embodiments, Xl 3 is selected from the group consisting of Thr, Sarc, Glu, Phe, Arg, Leu, Lys,? HAla, Aib, Lys (Ac), Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, to be. In certain embodiments, X13 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, beta hAla or Aib.

In certain embodiments, X15 is GIy, Ser, Thr, Gln, Ala or Sarc, [beta] -Ala, GIu, Arg or Asn. In certain embodiments, X15 is GIy, Ser, Thr, Gln, Ala or Sarc.

In certain embodiments, X13 is present.

In certain embodiments, X13 and X14 are present.

In certain embodiments, X13, X14, and X15 are present.

In certain embodiments of the peptide inhibitor of SEQ ID &lt; RTI ID = 0.0 &gt; I, &lt; / RTI &gt; X comprises, or alternatively consists of, a sequence of the following sequence Iq:

X1-X2-X3-C-X5-X6-W-X8-C-X10-X11-X12-X13-X14-

In this formula,

X1 is any amino acid, or is absent;

X2 is any amino acid, or is absent;

X3 is any amino acid or is absent;

X5 is selected from the group consisting of Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, D-Ala, D-Arg, D-Glu, D- Aib, D-Sarc,? -MeOrn,? -MeSer, Cit, Dap, Dab, Dap (Ac), Gly, Lys, Asn, N-MeGln, N-MeArg, Orn or Gln;

X6 is Asp, Thr, Asn, Phe, D-Asp, D-Thr, D-Asn, or D-Phe;

X8 is Val, Gln, Glu, or Lys;

X10 is Tyr, Phe, Phe (3,4- F 2), Phe (3,4-Cl 2), F (3-Me), Phe [4- ( 2-aminoethoxy)], Phe [4- (2- (acetyl-amino-ethoxy)], Phe (4-Br ), Phe (4-CONH 2), Phe (4-Cl), Phe (4-CN), Phe (4- guanidino), Phe (4-Me), Phe (4-NH 2), Phe (4-N 3), Phe (4-OMe), Phe (4-OBzl) or Tyr;

X11 is Trp, 1-Nal, 2- Nal ,, Phe (3,4-OMe 2) 5- hydroxy _{-Trp, Phe (3,4-Cl 2} ) or Tyr (3-t-Bu), and;

X12 is selected from the group consisting of His, Phe, Arg, N-Me-His, Val or D-His, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t- -MeLys (Ac),? -Me-Leu,? -MeOrn,? -MeSer (Ac) ,? -MeVal, Cha, Cit, Cpa, (D) Asn, Glu, hArg, or Lys;

X13 is either Thr, Sarc, Glu, Phe, Arg, Leu, Lys,? HAla, Val, Aib, Lys (Ac), Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, Orn, Gln, without doing;

X14 is Phe, Tyr,? HPhe, Asn, Arg, Qln, Lys (Ac), His; Dap (Ac), Dab (Ac), Asp, or absent;

X15 is GIy, Ser, Thr, Gln, Ala, Sarc, beta -Ala, GIu, Arg, Asn or is absent;

X16 is any amino acid, or is absent;

X17 is any amino acid or is absent;

X18 is any amino acid or is absent;

X19 is any amino acid, or is absent;

X20 is any amino acid, or is absent,

Here, Cys at position X4 and Cys at position X9 are arbitrarily linked.

In certain embodiments of Iq: X5 is selected from the group consisting of Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, D-Ala, D-Arg, D-Glu, D- , D-Ser, D-Aib, or D-Sarc; X10 is Tyr or Phe; X11 is Trp, 1-Nal, or 2-Nal; X12 is His, Phe, Arg, N-Me-His, Val or D-His, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t-butyl-Ala or t-butyl-Gly; X13 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys,? HAla, Val, Aib or is absent; X14 is Phe, Tyr,? HPhe, or is absent; X15 is Gly, Ser, Thr, Gln, Ala, Sarc, or is absent; X16 is Asp, Glu, Ala, AEA, AEP,? HAla, Gaba, Leu, or is absent; X17 is Leu, Lys, Arg, or is absent.

In certain embodiments, X 12 is selected from the group consisting of alpha amino acids such as 4-amino-4-carboxy-tetrahydropyran, Achc Acpc, Acbc, Acvc, Aib, ? -Me-Leu,? -MeOrn,? -MeSer,? -MeVal.

In certain embodiments, Xl 3 is selected from the group consisting of Thr, Sarc, Glu, Phe, Arg, Leu, Lys,? HAla, Aib, Lys (Ac), Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, to be. In certain embodiments, X13 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, beta hAla or Aib.

In certain embodiments, X 14 is Phe, Tyr,? HPhe, Asn, Arg, Qln, Lys (Ac), His; Dap (Ac), Dab (Ac), or Asp. In certain embodiments, X14 is Phe, Tyr, or? HPhe.

In certain embodiments, Xl 5 is GIy, Ser, Thr, Gln, Ala, Sarc, beta -Ala, GIu, Arg or Asn. In certain embodiments, X15 is GIy, Ser, Thr, Gln, Ala or Sarc.

In certain embodiments, X13 is present.

In certain embodiments, X13 and X14 are present.

In certain embodiments, X13, X14, and X15 are present.

In certain embodiments, Iq comprises, or alternatively consists of, a sequence of the sequence Iq '

X1-X2-X3-C-X5-X6-W-X8-C-X10-X11-X12-X13-X14-X15 (Iq '

Wherein X1-X14 have the definition provided for Iq,

Here, Cys at position X4 and Cys at position X9 are arbitrarily linked.

In certain embodiments of Iq ': X5 is selected from the group consisting of Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, D-Ala, D-Arg, D-Glu, D- Thr, D-Ser, D-Aib, or D-Sarc; X10 is Tyr or Phe; X11 is Trp, 1-Nal, or 2-Nal; X12 is His, Phe, Arg, N-Me-His, Val or D-His, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t-butyl-Ala or t-butyl-Gly; X13 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys,? HAla, Val, Aib or is absent; X14 is Phe, Tyr,? HPhe, or is absent; X15 is Gly, Ser, Thr, Gln, Ala, Sarc, or is absent; X16 is Asp, Glu, Ala, AEA, AEP,? HAla, Gaba, Leu, or is absent; X17 is Leu, Lys, Arg, or is absent.

In certain embodiments, Xl 3 is selected from the group consisting of Thr, Sarc, Glu, Phe, Arg, Leu, Lys,? HAla, Aib, Lys (Ac), Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, to be. In certain embodiments, X13 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, beta hAla or Aib.

In certain embodiments, X 14 is Phe, Tyr,? HPhe, Asn, Arg, Qln, Lys (Ac), His; Dap (Ac), Dab (Ac), or Asp. In certain embodiments, X14 is Phe, Tyr, or? HPhe.

In certain embodiments, X15 is GIy, Ser, Thr, Gln, Ala or Sarc, [beta] -Ala, GIu, Arg or Asn. In certain embodiments, X14 is Phe, Tyr, or? HPhe.

In certain embodiments, X13 is present.

In certain embodiments, X13 and X14 are present.

In certain embodiments, X13, X14, and X15 are present.

In certain embodiments of the peptide inhibitors of SEQ ID &lt; RTI ID = 0.0 &gt; I, &lt; / RTI &gt; X comprises or consists of a sequence of the following sequence Ir:

(Ir) X1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12-

In this formula,

X1 is any amino acid, or is absent;

X2 is any amino acid, or is absent;

X3 is any amino acid or is absent;

X4 is selected from the group consisting of Cys, Pen, hCys, D-Pen, D-Cys, D-hCys, Met, Glu, Asp, Lys, Orn, Dap, Dab, D-Dap, D- 3-chloro-butyric acid, 3-chloro-isobutyric acid, Abu, beta -D-Lys, Sec, 2-allyl glycine, 2- (3'-butenyl) glycine, 2- (4'-pentenyl) glycine, 2- (5'-hexenyl) glycine, Abu, or absent;

X5 is any amino acid;

X6 is any amino acid;

X7 is Trp, Glu, Gly, Ile, Asn, Pro, Arg, Thr or OctGly, or the corresponding? -Methylamino form of any of the foregoing;

X8 is any amino acid;

D-Dab, D-Dab, D-Asp, D-Glu, D-Lys, Asp, Leu, Val, Phe or Ser, Sec, Abu,? -Azido-Ala-OH, propargylglycine, 2-2-allylglycine, 2- (3'- '- pentenyl) glycine, Ala, hCys, Abu, Met, MeCys, (D) Tyr or 2- (5'- hexenyl) glycine;

X10 is Tyr, Phe (4-OMe), 1-Nal, 2-Nal, Aic,? -MePhe, Bip, (D) Cys, Cha, DMT, (D) Tyr, Glu, His, -dimethoxy), hTyr, N-Me- Tyr, Trp, Phe (4-CONH 2), Phe (4- phenoxy), Thr, Tic, Tyr ( 3-tBu), Phe (4-tBu), Phe (4-CN), Phe ( 4-Br), Phe (4-NH 2), Phe (4-F), Phe (3,5-F 2), Phe (4-CH 2 CO 2 H), Phe (penta -F), Phe (3,4-Cl 2), Phe (4-CF 3), Bip, Cha, 4- pyridyl alanine, βhTyr, OctGly, Phe (4 -N 3), Phe (4- Br), Phe [4- (2-aminoethoxy)] or Phe, Phe analogs, Tyr analogues, or the corresponding? -Methyl amino acid forms of any of the foregoing;

X11 is 2-Nal, 1-Nal, 2,4- dimethyl-Phe, Bip, Phe (3,4- Cl 2), Phe (3,4-F 2), Phe (4-CO 2 H), βhPhe ( 4-F), α-Me -Trp, 4- _{phenyl-cyclohexyl, Phe (4-CF 3)} ,, Phe (3,4-OMe 2), α-MePhe, βhNal, βhPhe, βhTyr, βhTrp, Nva ( 5-phenyl), Phe, His, hPhe, Tic, Tqa, Trp, Tyr, Phe (4-OMe), Phe Phe (4-OBzl), Octgly, Glu (Bzl), 4-phenylbenzylalanine, Phe (4-O) allyl, Tyr (3-tBu) (4-CONH ₂ ), Phe (4-CONH ₂ ), and Phe (2-aminoethoxy) Phe (3,4- _{dimethoxy), Phe (2,3-Cl 2} ), Phe (2,3-F 2), Phe (4-F), 4- phenyl-cyclohexyl alanine or Bip, or any of the Methyl amino acid form of &lt; / RTI &gt;

X12 is selected from the group consisting of His, Phe, Arg, N-Me-His or Val, Cav, Cpa, Leu, Cit, hLeu, 3-Pal, t- (D) Asp, (D) Leu, (D) Phe, (D) Tyr, Aib,? -MeLeu,? -MeOrn,? -Aib,? -Ala,? HAla,? HArg,? HLeu,? Gly, 4-amino-4-carboxy-tetrahydropyran, or N-MeLeu, Pig, Glu, hArg, Ile, Lys, N-MeLeu, N-MeArg, Ogl, Orn, Pro, Gln, Ser, Thr, ? -MeLys (Ac),? -Me-Leu,? -MeOrn,? -MeSer,? -MeVal, Cha, Cit, Cpa, (D) Asn, Glu, hArg, or Lys or the corresponding? -Methylamino form of any of the foregoing;

X13 is selected from the group consisting of Thr, Sarc, Glu, Phe, Arg, Leu, Asn, Cit, Lys, Arg, Orn, Val,? HAla, Lys (Ac) Chl, Asp, Dab, Dap,? -Diethyl Gly, hLeu, Asn, Ogl,? -Ph, Cha, Chg, Asp, Dab, Dlp, Thr, Ala,? -MeLeu, Aib,? -Ala,? -Glu,? HLeu,? HVal, , Pro, Gln, Ser,? -Spiro-pip, Thr, Tba, Tle or Aib, or the corresponding? -Methyl amino acid forms of any of the foregoing;

X14 is selected from the group consisting of Phe, Tyr, Glu, Gly, His, Lys, Leu, Met, Asn, Lys (Ac), Dap (Ac), Asp, Pro, Gln, Arg, Ser, Thr, Tic or? Methyl amino acid form of &lt; / RTI &gt;

Asp, (D) Leu, (D) Phe, (D) Thr, Aea, Asp, Asn, Glu, Glu, Ser, Thr, Gln, Ala, Phe, Gly, Lys, Leu, Pro, Arg, [beta] -Ala, or Sarc, or the corresponding [alpha] -methyl amino acid forms of any of the foregoing;

X16 is any amino acid, or is absent;

X17 is any amino acid or is absent;

X18 is any amino acid or is absent;

X19 is any amino acid, or is absent;

X20 is any amino acid or is absent.

In certain embodiments, the peptide is cyclized via X4 and X9.

In certain embodiments, X3 is Glu, D-Glu, Arg, (D) Arg, Phe, (D) Phe, 2-Nal, Thr, Leu, (D) Gln.

In certain embodiments of Ir: X11 is 2-Nal, 1-Nal, 2,4- dimethyl-Phe, Bip, Phe (3,4- Cl 2), Phe (3,4-F 2), Phe (4- _{CO 2 H), βhPhe (4} -F), α-Me-Trp, 4- _{phenyl-cyclohexyl, Phe (4-CF 3)} , α-MePhe, βhNal, βhPhe, βhTyr, βhTrp, Nva (5- phenyl) (4-O), Phe, His, hPhe, Tic, Tqa, Trp, Tyr, Phe ), Tyr (3-tBu), Phe (4-tBu), Phe (4-OBzl), Octgly, Glu (Bzl), 4-phenylbenzylalanine, Phe [4- (4-CONH ₂ ), Phe (3-amino-ethoxy)], 5-hydroxy-Trp, 6-chloro-Trp, N-MeTrp, 1,2,3,4-tetrahydro- _{4-dimethoxy), Phe (2,3-Cl 2} ), Phe (2,3-F 2), Phe (4-F), 4- phenyl-cyclohexyl alanine or Bip, or any of the equivalent to what MeLys, D-MeLys, &lt; / RTI &gt;&lt; RTI ID = 0.0 & Ala, (D) Asn, (D) Asp, (D) Leu, (D) Phe, (D) Tyr, Aib,? -MeLeu,? -MeOrn,? -Aib,? -Ala,? HAla,? HArg, , βh Val,? -Spiro-pip, Glu, hArg, Ile, Lys, N-MeLeu, N-MeArg, Ogl, Orn, Pro, Gln, Ser, Thr, Tle or t- (D) Asn, (D) Leu, (D) Leu, (D) Leu, Lys, Arg, Orn, Val, ) Phe, (D) Thr, Ala,? -MeLeu, Aib,? -Ala,? -Glu,? HLeu,? HVal,? -Spiro-piper, Cha, Chg, Asp, Dab, Dap, p-Thi, Tba, Tle or Aib, or the corresponding [alpha] -methyl amino acid forms of any of the foregoing; X14 is a corresponding? -Methyl amino acid form of any of Phe, Tyr, Glu, Gly, His, Lys, Leu, Met, Asn, Pro, Gln, Arg, Ser, Thr, Tic or? Asp, (D) Leu, (D) Phe, (D) Thr, Aea, Asp, Asn, Glu, Glu, Ser, Thr, Gln, Ala, Phe, Gly, Lys, Leu, Pro, Arg or Sarc, or the corresponding? -Methylamino form of any of the foregoing; X16 is Asp, Glu, Ala, AEA, AEP,? HAla, Gaba, Gly, Ser, Pro, Asn, Thr or absent or the corresponding? -Methylamino form of any of the foregoing; X17 is Leu, Lys, Arg, Glu, Ser, Gly, Gln, or is absent or is the corresponding? -Methylamino acid form of any of the foregoing.

In certain embodiments, X4 and X9 are both Pen. In certain embodiments, X4 and X9 are cyclized via a disulfide bond.

In certain embodiments, X4 is Abu and X9 is Cys. In certain embodiments, X4 and X9 are cyclized through a thioether linkage.

In certain embodiments, X5 is selected from the group consisting of Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, D-Ala, D-Arg, D-Glu, D-Phe, D- -Ser, D-Aib, Cys, Cit, Asp, Dab, Dap, Gly, His, hCys, Lys, Met, Asn, N-Me-Ala, Dys (Ac), Gly, Lys, Asn (SEQ ID NO: 1), Gly, Orn, Pro, Pen, Gln, Val, αMe-Lys, αMe-Orn or D-Sarc, α-MeOrn, , N-MeGln, N-MeArg, or Gln. In certain embodiments, X5 is Gln or Asn. In certain embodiments, X5 is selected from the group consisting of Ala, Arg, Glu, Phe, Leu, Thr, Ser, Aib, Sarc, D-Ala, D-Arg, D-Glu, D-Phe, D- -Ser, D-Aib, Cys, Cit, Asp, Dab, Dap, Gly, His, hCys, Lys, Met, Asn, N-Me-Ala, -Gln, N-Me-Arg, Orn, Pro, Pen, Gln, Val,? Me-Lys,? Me-Orn or D-Sarc. In certain embodiments, X5 is Gln.

In certain embodiments, X6 is Asp, Thr, Asn, Phe, D-Asp, D-Thr, D-Asn, Glu, Arg, Ser or D-Phe. In certain embodiments, X6 is Thr.

In certain embodiments, X7 is Trp.

In certain embodiments, X8 is Val, Gln, Glu, Phe, Asn, Pro, Arg, Thr, Trp or Lys. In certain embodiments, X8 is Gln.

In certain embodiments, X1, X2 and X3 are present.

In certain embodiments, X11 is a Trp analog.

In certain embodiments, X10 is a Phe analog. In certain embodiments, X10 is referred to as Phe (4-OMe), Phe (4-CONH 2), or Phe [4- (2- amino-ethoxy)] (also herein Phe [4-2ae); )to be. In certain embodiments, X10 is Phe (4-OMe) or Phe [4- (2-aminoethoxy)], also referred to herein as Phe [4-2ae).

In certain embodiments, X11 is 2-Nal or 1-Nal. In certain embodiments, X11 is 2-Nal.

In certain embodiments, X 12 is selected from the group consisting of? -MeLys, 4-amino-4-carboxy-tetrahydropyran, Acc Acpc, Acbc, Acvc, Agp, Aib, ,? -Me-Leu,? -MeOrn,? -MeSer, or? -MeVal. In certain embodiments, X 12 is? -MeLys.

In certain embodiments, X13 is Glu or Lys (Ac). In certain embodiments, X13 is GIu.

In certain embodiments, X14 is Asn.

In certain embodiments, X15 is Gly or Asn. In certain embodiments, X15 is GIy.

In certain embodiments, no more than one, no more than two, no more than three, or no more than four of X16, X17, X18, X19 and X20 are present. In certain embodiments, X16, X17, X18, X19, and X20 are absent.

In certain embodiments of Ir, X4 and X9 are Cys, X7 is Trp, and X18 is [(D) Lys]. In certain embodiments of Ir, X4 and X9 are Cys, X7 is Trp, X10 is Tyr, and X18 is [(D) Lys]. In certain embodiments of Ir, X4 and X9 are Cys, X7 is Trp, X1, X2 and X3 are absent, X17 is absent, X18 is [(D) Lys], X19 and X20 are present I never do that. In certain embodiments of Ir, X4 and X9 are Cys, X7 and X11 are Trp, X10 is Tyr, and X18 is [(D) Lys. In certain embodiments, X1, X2, and X3 are absent; In certain embodiments, X17 is absent.

In certain embodiments of Ir, X4 and X9 are Pen and X12 is a-MeLys. In certain embodiments of Ir, X4 and X9 are Pen, X12 is a-MeLys, and X16, X17, X18, X19, and X20 are absent. In certain embodiments of Ir, X4 and X9 are Pen and X12 is selected from the group consisting of alpha-MeLys, 4-amino-4-carboxy-tetrahydropyran, Achc Acpc, Acbc, Acvc, Agp, Aib, -MeLys (Ac),? -Me-Leu,? -MeOrn,? -MeSer,? -MeVal, X16, X17, X18, X19 and X20 are absent and X7 is Trp. In certain embodiments of Ir, X4 and X9 are Pen, X12 is? -MeLys, X16, X17, X18, X19 and X20 are absent and X7 is Trp. In certain embodiments of Ir, X4 and X9 are Pen, X7 is Trp, and X12 is a-MeLys. In certain embodiments, X1, X2, and X3 are absent. In certain embodiments, there is a disulfide bond between X4 and X9.

In certain embodiments of Ir, X4 is Abu, X9 is Cys and X12 is 4-amino-4-carboxy-tetrahydropyran, Achc Acpc, Acbc, Acvc, Agp, Aib, , Or? -MeLys (Ac),? -Me-Leu,? -MeOrn,? -MeSer, or? -MeVal. In certain embodiments of Ir, X4 is Abu, X9 is Cys, and X12 is [alpha] -MeLys. In certain embodiments of Ir, X4 is Abu, X9 is Cys, and X12 is selected from the group consisting of alpha-MeLys, 4-amino-4-carboxy-tetrahydropyran, Achc Acpc, Acbc, Acvc, Agp, Gly,? -MeLys, or? -MeLys (Ac),? -Me-Leu,? -MeOrn,? -MeSer, or? -MeVal and X16, X17, X18, X19 and X20 are absent. In certain embodiments of Ir, X4 is Abu, X9 is Cys, X12 is a-MeLys, and X16, X17, X18, X19, and X20 are absent. In certain embodiments of Ir, X4 is Abu, X9 is Cys, and X12 is selected from the group consisting of alpha-MeLys, 4-amino-4-carboxy-tetrahydropyran, Achc Acpc, Acbc, Acvc, Agp, Xyl, Ac-MeLys or? -MeLys (Ac),? -Me-Leu,? -MeOrn,? -MeSer or? -MeVal, X16, X17, X18, X19 and X20 are absent and X7 is Trp. In certain embodiments of Ir, X4 is Abu, X9 is Cys, X12 is? -MeLys, X16, X17, X18, X19, and X20 are absent and X7 is Trp. In certain embodiments of Ir, X4 is Abu, X9 is Cys, X7 is Trp, and X12 is [alpha] -MeLys. In certain embodiments, X1, X2, and X3 are absent. In certain embodiments, there is a thioether bond between X4 and X9.

In certain embodiments of the sequence I peptides inhibitor, X comprises or consists of a sequence of the following sequence is Is:

X1-X2-X3-C-X5-X6-W-X8-C-X10-X11-X12-X13-X14-

In this formula,

X1 is any amino acid, or is absent;

X2 is any amino acid, or is absent;

X3 is any amino acid or is absent;

X5 is any amino acid;

X6 is any amino acid;

X8 is any amino acid;

X10 is Tyr, 1-Nal 2-Nal , Phe (3,4-F 2), Phe (3,4-Cl 2), F (3-Me), Phe [4- ( 2-aminoethoxy)] , Phe [4- (2- (acetyl-amino-ethoxy)], Phe (4-Br ), Phe (4-CONH 2), Phe (4-Cl), Phe (4-CN), Phe (4- guanidino), Phe (4-Me) , Phe (4-NH 2), Phe (4-N 3), Phe (4-OMe), Phe (4-OBzl) or Tyr;

X11 is Trp 1-Nal, Phe (3,4-OMe ₂ ) 5-hydroxy-Trp, Phe (3,4-Cl ₂ ) or Tyr (3-t-Bu);

X12 is selected from the group consisting of Arg, Lys, His, hArg, Cit, Orn, 1-Nal, D-Ala, D- Leu, D-Phe, D- Asn, D- Asp, Agp, Leu,? HLeu, Aib,? HAla,? HVal, MeLys,? -MeLys (Ac),? -MeLys,? -MeLys (Ac),? -MeLys Leu,? -MeOrn,? -MeSer,? -MeVal, Cha, Cit, Cpa, (D) Asn, Glu, hArg, or Lys;

Lys (Ac), Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, Orn, Lys Ac), or Gln;

X14 is Phe, Tic, Asn Tyr, Asn, Arg, Qln, Lys (Ac), His; Dap (Ac), Dab (Ac), or Asp;

X16 is any amino acid;

X17 is absent;

X18 is D-Lys

X19 is any amino acid, or is absent;

X20 is any amino acid or is absent.

In certain embodiments of Is: X10 is Tyr, 1-Nal or 2-Nal; X11 is Trp or 1-Nal; X12 is selected from the group consisting of Arg, Lys, His, hArg, Cit, Orn, 1-Nal, D-Ala, D- Leu, D-Phe, D- Asn, D- Asp, Agp, Leu,? HLeu, Aib,? HAla,? HVal, beta hArg, hLeu or Dap; X13 is Cha, Ogl, Aib, Leu, Val, Dab, Glu, Lys,? HLeu,? HAla,? HVal or? X14 is Phe, Tic, Asn or Tyr; X16 is AEA, Ala or [beta] Ala.

In certain embodiments: X5 is selected from the group consisting of Glu, Arg, Ala, N-Me-Arg, N-Me-Ala, N-Me-Gln, Orn, N-Me- , Asn, or Dap. In certain embodiments, X5 is selected from the group consisting of Glu, Arg, Ala, N-Me-Arg, N-Me-Ala, N-Me-Gln, Orn, N-Me- to be.

In certain embodiments, X6 is Asp or Thr.

In certain embodiments, X8 is Gln or Val.

In certain embodiments, the peptide of Is is cyclized through a disulfide bond between X4 and X9.

In certain embodiments of the peptide inhibitors of SEQ ID &lt; RTI ID = 0.0 &gt; I, &lt; / RTI &gt; X comprises or consists of a sequence of the sequence It:

X @ 1 -X @ 2 --X @ 3 --C @ X @ 5 --X @ 6 --W - X @ 8 --C @

In this formula,

X1 is any amino acid, or is absent;

X2 is any amino acid, or is absent;

X3 is any amino acid or is absent;

X5 is any amino acid;

X6 is any amino acid;

X8 is any amino acid;

X10 is Tyr, 1-Nal, 2- Nal, Phe [4- ( 2-aminoethoxy)], Phe (4-CONH 2), Phe (4-OMe) , and;

X11 is Trp, 1-Nal, 2- Nal, Bip ,, Phe (3,4-OMe 2) 5- hydroxy -Trp gt;

X12 is selected from the group consisting of Arg, His, 3-Pal, Leu, Thr, Gln, Asn, Glu, Ile, Phe, Ser, Lys, hLeu,? -MeLeu, D- ? -MeLys (Ac),? -Me-Leu,? -MeOrn,? -MeSer or? -MeLeR alpha -MeVal;

X13 is Thr, Glu, Tyr, Lys, Gln, Asn, Lys, Lys (Ac), Asp, Arg, Ala, Ser, Leu;

X14 is Phe, Tyr, Asn, Gly, Ser, Met, Arg, His, Lys, Leu or Gln;

X15 is Gly, Ser, Arg, Leu, Asp, Ala,? -Ala, Glu, Arg or Asn;

X16 is absent, or is any amino acid;

X17 is absent or is any amino acid;

X18 is any amino acid or is absent;

X19 is any amino acid, or is absent;

X20 is any amino acid or is absent.

In certain embodiments of It: X10 is Tyr, 1-Nal or 2-Nal; X11 is Trp, 1-Nal, 2-Nal or Bip; X12 is Arg, His, 3-Pal, Leu, Thr, Gln, Asn, Glu, Ile, Phe, Ser, Lys, hLeu,? -MeLeu, D-Leu, D-Asn or h-Leu; X13 is Thr, Glu, Tyr, Lys, Gln, Asn, Lys, Asp, Arg, Ala, Ser, Leu; X15 is GIy, Ser, Arg, Leu, Asp or Ala; X16 is absent or is Asn, Glu, Phe, Ala, Gly, Pro, Asp, Gln, Ser, Thr, D-Glu or Lys; X17 is absent or is Pro, Arg, Glu, Asp, Ser, Gly or Gln.

In certain embodiments, X5 is Ser, Asp, Asn, Gln, Ala, Met, Arg, His or Gly. In certain embodiments, X5 is Ser, Asp, Gln, Ala, Met, Arg, His or Gly.

In certain embodiments, X6 is any Asp, Ser, or Thr.

In certain embodiments, X8 is Gln, Glu, or Thr.

In certain embodiments, the peptide of It is cyclized through a disulfide bond between X4 and X9.

In a further embodiment, the invention provides a peptide inhibitor of the interleukin-23 receptor, or a pharmaceutically acceptable salt or solvate thereof, wherein the peptide inhibitor comprises the amino acid sequence of SEQ ID NO: Va:

X1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12-X13-X14-

In this formula,

X1 is any amino acid, or is absent;

X2 is any amino acid, or is absent;

X3 is any D-amino acid, or is absent;

X4 is a chemical moiety capable of forming a bond with Cys, hCys, Pen, hPen, Abu, Ser, hSer or X9;

X5 is Ala,? -MeOrn,? -MeSer, Cit, Dap, Dab, Dap (Ac), Gly, Lys, Asn, N-MeGln, N-MeArg, Orn, Gln, Arg, Ser or Thr;

X6 is Thr, Ser, Asp, Ile or any amino acid;

X7 is Trp, 6-chloro-Trp, 1-Nap or 2-Nap;

X8 is selected from the group consisting of Glu, Gln, Asn, Lys (Ac), Cit, Cav, Lys (N-epsilon- (N- alpha -palmitoyl- L- gamma -glutamyl) ;

X9 is a chemical moiety capable of forming a bond with Cys, hCys, Pen, hPen, Abu, or X4;

X10 is 2-Nal, Phe analog, Tyr, or Tyr analog;

X11 is 1-Nal, 2-Nal, Phe (3,4- dimethoxy), _{5-hydroxy-Trp, Phe (3,4-Cl 2} ), Trp or Tyr (3-tBu), and;

X12 is selected from the group consisting of Aib, 4-amino-4-carboxy-tetrahydropyran, any alpha-methyl amino acid, alpha-ethyl-amino acid, Achc, Acvc, Acbc Acpc, Me, Me, Al, Me, Ca, Ca, Cpa, D-Asn, , Glu, His, hLeu, hArg, Lys, Leu, Octgly, Orn, piperidine, Arg, Ser, Thr or THP;

X13 is Lys (Ac), Gln, Cit, Glu, or any amino acid;

X14 is selected from the group consisting of Asn, Gln, Lys (Ac), Cit, Cav, Lys (N-epsilon- (N-alpha-palmitoyl- L- gamma- glutamyl) &Lt; / RTI &gt;

X15 is? -Ala, Asn, Gly, Gln, Ala, Ser, Aib or Cit;

X16 is any amino acid, or is absent;

X17 is any amino acid or is absent;

X18 is any amino acid or is absent;

X19 is any amino acid, or is absent;

X20 is any amino acid, or is absent;

Here, X4 and X9 may form a bond with each other. In certain embodiments, the bond is an ether, a disulfide bond or a thioether bond. In certain embodiments, the peptide inhibitor is cyclized via a bond between X4 and X9.

In certain embodiments, Xl is a D-amino acid or is absent. In certain embodiments, X2 is a D-amino acid or is absent.

In certain embodiments, X16 is a D-amino acid or is absent. In certain embodiments, X17 is a D-amino acid, or is absent. In certain embodiments, X18 is a D-amino acid or is absent. In certain embodiments, X19 is a D-amino acid or is absent. In certain embodiments, X20 is a D-amino acid or is absent.

In certain embodiments of the sequence formula (Ia), X10 is 2-Nal, Phe (3,4- diF 2), Phe (3,4-Cl 2), Phe (3-Me), Phe [4- (2 Phe (4-CONH2), Phe (Cl), Phe (4-CN), Phe (4-guanyloxy) (4-Me), Phe (4-NH ₂ ), Phe (4-N ₃ ), Tyr, Tyr (Bzl), or Tyr (Me). In certain embodiments of the sequence formula (Ia), and X10 is Phe (4-ZR), Phe (3-ZR), or Phe (2-ZR), wherein _{R = CH 2 (CH 2)} n Y, n a = 1 to 25 and, Z = NH, O, CO , CONH, or CH _{2 and, = NH 2, CO 2 H} , OH, or CH _3.

In a further related embodiment, the invention comprises a peptide inhibitor of the interleukin-23 receptor, or a pharmaceutically acceptable salt or solvate thereof, wherein the peptide inhibitor comprises the amino acid sequence of the sequence formula (Vb):

(Vb) X 1 -X 2 -X 3 -X 4 -X 5 -X 6 -X 7 -X 8 -X 9 -X 10 -X 11 -X 12 -X 13 -X 14 -X 15 -X 16 -X 17 -X 18 -X 19-

In this formula,

X1 is any amino acid, or is absent;

X2 is any amino acid, or is absent;

X3 is D-Arg, D-Phe, any D amino acid, or is absent;

X4 is a chemical moiety capable of forming a bond with Cys, hCys, Pen, hPen, Abu, or X9;

X5 is Gln, Asn, Lys (Ac), Cit, Cav, Lys (N-epsilon- (N-alpha-palmitoyl-L-gamma -glutamyl)) or Lys (N-epsilon-palmitoyl);

X6 is Thr, Ser, Asp, Ile or any amino acid;

X7 is Trp, 1-Nap or 2-Nap;

X8 is Gln, Asn, Lys (Ac), Cit, Cav, Lys (N-epsilon- (N-alpha-palmitoyl-L-gamma -glutamyl)) or Lys (N-epsilon-palmitoyl);

X9 is any amino acid or chemical moiety capable of forming a bond with Cys, hCys, Pen, hPen, Abu, X4;

X10 is Phe [4- (2-amino-ethoxy)], Phe [4- (2-acetylamino-ethoxy)], Phe (4-CONH 2), Phe (4- guar dino), Phe (4-NH ₂ ), Tyr (Me) or Phe (4-ZR), where R = CH ₂ (CH ₂ ) _n Y; n = 1-25; Z = O, CO, NH, CONH, or CH ₂ ; _{Y = NH 2, CO 2 H} , OH, or CH _3, and;

X11 is 2-Nal or Trp;

X12 is selected from the group consisting of Aib, 4-amino-4-carboxy-tetrahydropyran, alpha -dialethyl Gly, alpha-MeLys, alpha-MeLys (Ac), alpha-MeLeu, alpha-MeOrn, , Achc, Acvc, Acbc Acpc, or 4-amino-4-carboxy-piperidine;

X13 is Lys (Ac), Gln, Cit, Glu, or any amino acid;

X14 is selected from the group consisting of Asn, Gln, Lys (Ac), Cit, Cav, Lys (N-epsilon- (N-alpha-palmitoyl- L- gamma- glutamyl) &Lt; / RTI &gt;

X15 is? -Ala, Asn, Gln, Ala, Ser, or Aib;

X16 is any amino acid, or is absent;

X17 is any amino acid or is absent;

X18 is any amino acid or is absent;

X19 is any amino acid, or is absent;

X20 is any amino acid, or is absent;

Here, X4 and X9 may form a bond with each other. In certain embodiments, the bond is a disulfide bond or a thioether bond. In certain embodiments, the peptide inhibitor is cyclized via a bond between X4 and X9.

In certain embodiments, Xl is a D-amino acid or is absent. In certain embodiments, X2 is a D-amino acid or is absent.

In certain embodiments, X16 is a D-amino acid or is absent. In certain embodiments, X17 is a D-amino acid, or is absent. In certain embodiments, X18 is a D-amino acid or is absent. In certain embodiments, X19 is a D-amino acid or is absent. In certain embodiments, X20 is a D-amino acid or is absent.

In another related embodiment, the invention includes a peptide inhibitor of the interleukin-23 receptor, or a pharmaceutically acceptable salt or solvate thereof, wherein the peptide inhibitor comprises the amino acid sequence of the sequence formula (Vc):

(Vc) X1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12-

In this formula,

X1 is absent;

X2 is absent;

X3 is D-Arg, or is absent;

X4 is a chemical moiety capable of forming a bond with Cys, Pen, Abu or X9;

X5 is Gln, Asn, Lys (Ac), Cit, or Cav;

X6 is Thr or Ser;

X7 is Trp, 1-Nap or 2-Nap;

X8 is Gln, Asn, Lys (Ac), Cit, or Cav;

X9 is any amino acid or chemical moiety capable of forming a bond with Cys, hCys, Pen, hPen, Abu, or X4;

X10 is Phe [4- (2- amino-ethoxy)], Phe (4-CONH2 ) , or Phe (4-OR), _{wherein, R = CH 2 (CH 2} ) n Y , and; n = 1-25; _{Y = NH 2, CO 2 H} , OH, or CH _3, and;

X11 is Trp or 2-Nal;

X12 is Aib, 4-amino-4-carboxy-tetrahydropyran, alpha-MeLys, alpha-MeLys (Ac), alpha-MeLeu, Achc, Acvc, Acbc or Acpc;

X13 is Lys (Ac) or GIu;

X14 is Asn, Gln, Lys (Ac), Lys (N-epsilon- (N-alpha-palmitoyl-L- gamma -glutamyl)) or Lys (N-epsilon-palmitoyl);

X15 is Gly,? -Ala, Asn, Gln, Ala, Ser, or Aib;

X16 is absent;

X17 is absent;

X18 is absent;

X19 is absent;

X20 is absent;

Here, X4 and X9 may form a bond with each other. In certain embodiments, the bond is a disulfide bond or a thioether bond. In certain embodiments, the peptide inhibitor is cyclized via a bond between X4 and X9.

In certain embodiments, Xl is a D-amino acid or is absent. In certain embodiments, X2 is a D-amino acid or is absent.

In certain embodiments, X16 is a D-amino acid or is absent. In certain embodiments, X17 is a D-amino acid, or is absent. In certain embodiments, X18 is a D-amino acid or is absent. In certain embodiments, X19 is a D-amino acid or is absent. In certain embodiments, X20 is a D-amino acid or is absent.

In another related embodiment, the invention includes a peptide inhibitor of the interleukin-23 receptor, or a pharmaceutically acceptable salt or solvate thereof, wherein the peptide inhibitor comprises the amino acid sequence of the sequence formula (Vd):

(Vd) X1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12-

In this formula,

X1 is absent;

X2 is absent;

X3 is absent;

X4 is Pen or Abu;

X5 is Gln or Asn;

X6 is Thr or Ser;

X7 is Trp;

X8 is Gln or Asn;

X9 is Pen or Cys;

X10 is Phe [4- (2-aminoethoxy) or Phe (4-CONH ₂₎ and;

X11 is Trp or 2-Nal;

X12 is Aib, 4-amino-4-carboxy-tetrahydropyran,? -MeLys,? -MeLeu, or Achc;

X13 is Lys (Ac) or GIu;

X14 is Asn, Gln or Lys (Ac);

X15 is Gly, Ala, Ser, [beta] -Ala, Asn, or Gln;

X16 is absent;

X17 is absent;

X18 is absent;

X19 is absent;

X20 is absent;

Here, X4 and X9 may form a bond with each other. In certain embodiments, the bond is a disulfide bond or a thioether bond. In certain embodiments, the peptide inhibitor is cyclized via a bond between X4 and X9.

Any of the peptide inhibitors of the present invention (e.g., any of the sequence I (eg, Ix, Ia-It)) can be further defined, eg, as described below. Each of the further defined features described herein can be applied to any peptide inhibitor, where it is understood that the amino acid assigned at a particular position allows for the presence of additional defined features.

In certain embodiments, any Phe [4- (2-aminoethoxy)] residue present in the peptide inhibitor may be substituted with Phe [4- (2-acetylaminoethoxy)].

In certain embodiments, Xl to X20 are any amino acids that appear at corresponding positions to the cyclized Pen-Pen or the cyclized Abu-Cys residue of the exemplary peptide inhibitor shown in Tables 2-5.

In certain embodiments, peptide inhibitors of the sequence formula (X), (Va), (Vb), (Vc), (Vd), (Ve), (Vf), (Vg) Any of the peptide inhibitors described herein that do not further comprise a linker or spacer moiety between any two peptide amino acid residues. In certain embodiments, the linker or spacer moiety is a PEG moiety.

In certain embodiments, the peptide inhibitor is cyclized by a disulfide bridge.

In certain embodiments, X10 is Tyr, Phe [4- (2-aminoethoxy)], Phe (4-CONH 2) , or Phe (4-OMe). In certain embodiments, XlO is Tyr.

In certain embodiments, X11 is 2-Nal, Trp, or 5-hydroxy-Trp. In certain embodiments, X11 is Trp.

In certain embodiments, X10 is Tyr or Phe [4- (2-aminoethoxy)] and X11 is Trp or 2-Nal. In certain embodiments, X10 is Tyr and X11 is Trp.

In certain embodiments, X4 and X9, both are Cys.

In certain embodiments, X4 is Cys, Pen, hCys, or is absent.

In certain embodiments, X7 and X11 are both not W.

In certain embodiments, X7 and X11 are both W.

In certain embodiments, X7 and X11 are both W, X10 is Y, and X4 and X9 are both Cys.

In certain embodiments, X15 is Gly, Asn, beta-ala or Ser. In certain embodiments, X15 is GIy or Ser.

In certain embodiments, X16 is AEA or AEP.

In certain embodiments, X10 is Tyr, Phe or Phe [4- (2-aminoethoxy). In certain embodiments, XlO is Tyr or Phe.

In certain embodiments, X11 is Trp or 2-Nal. In certain embodiments, X11 is Trp.

In certain embodiments, X1, X2, and X3 are absent.

In certain embodiments, X18, X19, and X20 are absent.

In certain embodiments, X1, X2, X3, X18, X19, and X20 are absent.

In certain embodiments, at least one of Xl, X2, or X3 is present.

In certain embodiments of any of Ix, Ia-Ir, one of Xl, X2 and X3 is present and the other two are absent. In one embodiment, X1, X2 or X3 present is Ala.

In certain embodiments, X3 is present. In certain embodiments, X3 is Glu, (D) Glu, Arg, (D) Arg, Phe, (D) Phe, 2-Nal, Thr, Leu, (D) Gln. In certain embodiments, X3 is (D) Arg or (D) Phe. In certain embodiments, X1 and X2 are absent and X3 is present.

In certain embodiments, two of X1, X2 and X3 are present and the other is absent. In certain embodiments, the two present are comprised of SG, NK, DA, PE, QV or DR.

In certain embodiments, X1, X2 and X3 are present. In certain embodiments, X1, X2, and X3 comprise ADQ, KEN, VQE, GEE, DGF, NAD, ERN, RVG, KAN, or YED.

In certain embodiments, the peptide comprises an AEP residue. In certain embodiments, any of X15, X16, X17, X18, X19, or X20 is AEP.

In certain embodiments of any of the peptide inhibitor or peptide monomer subunits, X13 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, Lys (Ac), beta hAla, or Aib. In certain embodiments of any of the peptide inhibitor or peptide monomer subunits, X13 is Thr, Sarc, Glu, Phe, Arg, Leu, Lys, beta hAla, or Aib. In certain embodiments, X14 is Phe, Asn, Tyr, or? HPhe. In certain embodiments, X14 is Phe, Tyr, or? HPhe. In certain embodiments, X15 is Gly, Asn Ser, Thr, Gln, Ala, or Sarc. In certain embodiments, X15 is GIy, Ser, Thr, Gln, Ala, or Sarc. In certain embodiments, X 12 is selected from the group consisting of alpha amino acids such as 4-amino-4-carboxy-tetrahydropyran, Achc Acpc, Acbc, Acvc, Aib, ? -Me-Leu,? -MeOrn,? -MeSer, or? -MeVal.

In certain embodiments, X13 is present.

In certain embodiments, X13 and 14 are present.

In certain embodiments, X13, X14, and X15 are present.

In certain embodiments of any of Ia-It, there is at least one of X16-X20. In certain embodiments, there are two or more, or three or more, of X16-X20. In certain embodiments, X18 is [(D) Lys]. In certain embodiments, X17 is absent and X18 is [(D) Lys]. In certain embodiments wherein X4 and X9 are optionally Cys, X4 and X9 are Cys, X7 is Trp, and X18 is [(D) Lys]. (X) and X9 are optionally Cys, X4 and X9 are Cys, X7 is Trp, X10 is Tyr or Phe [4- (2-aminoethoxy) ]to be. In certain embodiments, X4 and X9 are optionally Cys, X4 and X9 are Cys, X7 is Trp, X10 is and X18 is [(D) Lys]. X4 and X9 are optionally Cys, X4 and X9 are Cys, X7 is Trp, X1, X2 and X3 are absent, X17 is absent, X18 is [(D) Lys] , X19 and X20 do not exist. In certain embodiments of Ir, X4 and X9 are Cys, X7 and X11 are Trp, X10 is Tyr, and X18 is [(D) Lys. In certain embodiments, X1, X2, and X3 are absent; In certain embodiments, X17 is absent.

In certain embodiments, any of the peptide inhibitors (or monomer subunits) described herein is cyclized. In certain embodiments, the peptide inhibitor is a ring closure through a bond between two or more internal amino acids of the peptide inhibitor. In certain embodiments, the cyclized peptide inhibitor is not cyclized via a bond between the N-terminal and C-terminal amino acids of the peptide inhibitor. In certain embodiments, one of the amino acid residues participating in an intramolecular bond cyclizes the peptide at the amino terminal amino acid residue. In certain embodiments, any of the peptide inhibitors is cyclized through a peptide bond between its N-terminal amino acid and its C-terminal amino acid.

(Or one or both of its monomer subunits) is linked to a peptide inhibitor, or a monomer subunit thereof, via an intramolecular bond between X4 and X9, or via a triazole And is ring-closed by a ring. In certain embodiments, the intramolecular bond is any disulfide bond, a thioether bond, a lactam bond, a triazole, a selenoether bond, a diselenide bond, or an olefin bond.

In one embodiment, X4 and X9 of the peptide inhibitor (or one or both of its monomer subunits) are Cys, Pen, hCys, D-Pen, D-Cys or D-hCys, to be. In certain embodiments, X4 and X9, both are Cys, or X4 and X9, both are Pen, and the intramolecular bond is a disulfide bond.

In one embodiment, X4 and X9 of the peptide inhibitor (or one or both of its monomer subunits) are selected from the group consisting of Glu, Asp, Lys, Orn, Dap, Dab, D-Dap, D- Glu or D-Lys, and the intramolecular bond is a lactam bond.

In one embodiment, X4 is selected from the group consisting of Abu, 2-chloromethylbenzoic acid, mercapto-propionic acid, methapto-butyric acid, 2-chloro-acetic acid, 3- chloropropionic acid, 4- chlorobutyric acid, ego; X9 is Abu, Cys, Pen, hCys, D-Pen, D-Cys or D-hCys; The intramolecular bond is a thioether bond. In certain embodiments, X4 is Abu, X9 is Pen, and the intramolecular bond is a thioether bond. In certain embodiments, X4 is a 2-methylbenzoyl moiety capable of forming a thioether linkage with X9 and X9 is selected from Cys, N-Me-Cys, D-Cys, hCys, Pen, and D-Pen . In certain embodiments, X4 is Abu, X9 is Cys, and the intramolecular bond is a thioether bond. In certain instances, in the peptide monomers, dimers, or subunits thereof of any of the sequences and peptides described herein, X4 is selected from the group consisting of modified Ser, modified hSer (e.g., homo-Ser-Cl) , And corresponding D-amino acids. In other cases, X4 is an aliphatic acid having 1 to 4 carbons and capable of forming a thioether bond with X9. In some cases, X4 is a 5- to 6-membered alicyclic acid having a modified 2-methyl group that forms a thioether bond with X9. In some embodiments, X4 is a 2-methylbenzoyl moiety. In certain embodiments, X4 is selected from Cys, hCys, Pen, and a 2-methylbenzoyl moiety. In certain embodiments, X4 is selected from the group consisting of modified Ser, modified hSer, suitable copper scaffolds, and corresponding D-amino acids. In one embodiment, X4 is hSerCl (prior to the formation of a thioether bond with X9, thereby eliminating Cl) or hSer precursor (e.g., O-TBDMS) In some cases, X &lt; 4 &gt; is a 5- to 6-membered alicyclic acid having a modified 2-methyl group which forms a thioether bond with X &lt; 9 & X4 is a 2-methylbenzoyl moiety. In certain embodiments wherein X4 is a chemical moiety that binds to X9, rather than an amino acid, X1, X2, and X3 are absent and X4 is joined to X5, In certain embodiments, X4 is an amino acid while in other embodiments, X4 is bonded to X9 to form, for example, a thioether bond &lt; RTI ID = 0.0 &gt; Can form X4 is another chemical moiety selected from any of the non-amino acid moieties described herein for X4. It is also to be understood that when X4 is another chemical moiety, In an embodiment, X1, X2 and X3 are absent and another chemical moiety is attached to, or conjugated to, X5. In certain embodiments, X4 is a group such as a chloride, such as 2-chloromethylbenzoic acid Is defined as a chemical moiety, including 2-chloro-acetic acid, 3-chloropropionic acid, 4-chlorobutyric acid, 3-chloroisobutyric acid. However, once the peptide has undergo cyclocyclization, It will be appreciated by those skilled in the art that the chloride group is no longer present after formation of X4. The description of the chemical moiety means both a group containing chloride and also a group that does not contain chloride, i.e., after formation of a bond with X9. The invention also includes any of the other sequences or tables described herein , Wherein the thioether linkage is a reverse orientation. In this embodiment of the invention, in general, the amino acid residues or other chemical moieties presented at X4 are instead present at X9 and the amino acid residues presented at X9 are instead present at X4, i.e. the sulfur of the resulting thioether linkage It can be considered that the containing amino acid residue is located at X4 instead of X9 and that the amino acid residue or other moiety having a carbon side chain capable of forming a thioether bond with X4 is located at X9. However, in this reverse orientation, the amino acid or chemical moiety at position X9 is free amine. For example, in certain embodiments, the amino acid of X9 is a protected homoserine, such as, for example, homoserine (OTBDMS). Thus, in certain embodiments reverse orientation of the peptide inhibitor of any of the sequences set forth herein, X9 is an amino acid residue having a side chain comprising one or two carbons and forming a thioether bond with X4, and X4 Is selected from the group consisting of Cys, N-Me-Cys, D-Cys, HCys, Pen, and D-Pen. Specific examples of other sequence and amino acid residues and other chemical moieties present at corresponding positions in the table are described herein.

Those skilled in the art will appreciate that certain amino acids and other chemical moieties are modified when attached to another molecule. For example, an amino acid side chain can be modified when forming an intramolecular bridge with another amino acid side chain, for example, one or more hydrogens can be removed or replaced by a bond. In addition, when hSer-Cl binds to an amino acid such as Cys or Pen through a thioether bond, the Cl moiety is liberated. Thus, as used herein, reference to an amino acid or a modified amino acid, such as hSer-Cl, present in a peptide dimer of the invention (e. G. At position X4 or position X9) Quot; is meant to include the formation of said amino acid or modified amino acid present in the peptide both after formation thereof.

In certain embodiments, the peptide inhibitor (or one or both of its monomer subunits) of the peptide inhibitor is one that is cyclized through the triazole ring. In certain embodiments, the peptide inhibitor (or one or both of its monomer subunits) of the peptide inhibitor is linear or non-cyclized. In certain embodiments of any of the peptide inhibitors described herein, including both monomeric peptide inhibitors and dimeric peptide inhibitors, one (or both) of the peptide monomer subunits comprises Ix, Ia, Ib, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, Il, Im, In, Io, Ip, Iq, Iq ', Ir, Is or It, IIa-IId, IIIa-IIIe, Iva or IVb Or comprises, a cyclized peptide having the structure or sequence described in any of the above.

In certain embodiments of any of the peptide inhibitors or monomer subunits, X7 and X11 are both W.

In certain embodiments of any of the peptide inhibitors or monomeric subunits, X7 and X11 are not both W. In certain embodiments, X7 is W and X11 is not W.

In certain embodiments of any of the peptide inhibitor or monomer subunits, X4 and X9 form an intramolecular bond between the moieties that is a thioether bond, a lactam bond, a triazole, a selenoether, a diselenide bond, or an olefin bond It is an amino acid residue that can be made.

In certain embodiments, wherein X7 and X11, both of W, X10 is Y, Phe [4- and (2-amino-ethoxy) or Phe (CONH _2), X4 and X9 is a thioether bond between each other, a lactam bond , A triazole, a selenoether, a diselenide bond, or an olefin bond. In certain embodiments, X7 and X11 are both W, X10 is Y, and X4 and X9 are selected from the group consisting of a thioether bond, a lactam bond, a triazole, a selenoether, a diselenide bond, Is an amino acid residue capable of forming an internal bond.

In certain embodiments, X7 and X11 are both W, X10 is Y, X4 and X9 are both C.

In certain embodiments, X4 and X9 are Cys, Pen, hCys, D-Pen, D-Cys or D-hCys, respectively, and the intramolecular bond is a disulfide bond.

In certain embodiments, X4 and X9 are each a Glu, Asp, Lys, Orn, Dap, Dab, D-Dap, D-Dab, D-Asp, D-Glu or D-Lys, .

In certain embodiments, X4 and X9 are each? -Azido-Ala-OH or propargylglycine, and the peptide inhibitor (or monomer subunit) is cyclized via a triazole ring.

In certain embodiments, X4 and X9 are each 2-allyl glycine, 2- (3'-butenyl) glycine, 2- (4'-pentenyl) glycine, or 2- (5'- The peptide inhibitor (or monomer subunit) is cyclized via ring-closing metathesis, thereby yielding the corresponding olefin / "stapled peptide".

In certain embodiments, X4 is selected from the group consisting of 2-chloromethylbenzoic acid, methapto-propionic acid, methapto-butyric acid, 2- chloro-acetic acid, 3- chloro- propionic acid, 4- chlorobutyric acid, 3- chloroisobutyric acid, (Cl); X9 is hSer (Cl), Cys, Pen, hCys, D-Pen, D-Cys or D-hCys; The intramolecular bond is a thioether bond. In certain embodiments, X4 is 2-chloromethylbenzoic acid or hSer (Cl); X9 is Cys or Pen, and the intramolecular bond is a thioether bond. In certain embodiments, X4 is Abu and X9 is Cys or Pen.

In certain embodiments, X4 is 2-chloromethylbenzoic acid, 2-chloro-acetic acid, 3-chloro- propionic acid, 4-chloro- butyric acid, 3-chloro-isobutyric acid, Abu or Sec; X9 is Abu or Sec; The intramolecular bond is a selenoether bond.

In certain embodiments, the intramolecular bond between X4 and X9 is a diselenide bond.

In certain embodiments of any of the peptide inhibitors described herein that contain two amino acid residues, such as cysteine residues, joined by an intramolecular bond, e.g., a disulfide bond, two amino acid residues participating in the intramolecular bond Are neither located at the N-terminal or C-terminal position of the peptide inhibitor. In certain embodiments, neither of the two amino acid residues involved in intramolecular binding, such as cysteine, is located at the N-terminal or C-terminal position of the peptide inhibitor. In other words, in certain embodiments, at least one, or both, of the two amino acid residues, such as cysteine, participating in an intramolecular bond are internal amino acid residues of the peptide inhibitor. In certain embodiments, neither of the two amino acid residues involved in intramolecular binding, such as cysteine, is located at the C-terminal position of the peptide inhibitor. In certain embodiments, the two amino acid residues involved in intramolecular binding are Cys, Pen, hCys, D-Pen, D-Cys or D-hCys residues. In certain embodiments, the two amino acid residues involved in intramolecular binding are located at X4 and X9. In one embodiment, there is a disulfide bond between the amino acid residues X4 and X9, e.g., cysteine or Pen residues. In certain embodiments, X4 and X9 are both Pen. In certain embodiments, the peptide monomer subunit of one or both of the peptide inhibitors is cyclized through a disulfide bond located between two Pen residues, e. G., X4 and X9.

In certain embodiments of any of the peptide inhibitors described herein, either monomeric or dimeric, one or both of the peptide monomer subunits present in the peptide inhibitor may be present in the peptide monomer or peptide monomer subunit, for example, Or an intramolecular bond between two cysteine residues, such as a disulfide bond. In certain embodiments, the peptide inhibitor comprises two or more cysteine residues. In some embodiments, the peptide inhibitor is one that is cyclized through an intramolecular disulfide bond between the two cysteine residues. In certain embodiments of the peptide inhibitors having any of the sequence formulas described herein, two cystines are present at positions X4 and X9. In another embodiment, one or both of the peptide monomer subunits of the peptide inhibitor is, for example, cyclized through a disulfide bond between the two Pen residues at positions X4 and X9.

In some embodiments, the peptide inhibitor has the structure of any of the sequence formula (eg, SEQ ID NO: I) described herein and includes a disulfide bond, eg, an intramolecular disulfide bond or a thioether bond. Exemplary examples of such peptide inhibitors are set forth in Tables 3a-3h and 4a, 4b, 9, 11, or 15. The disulfide-linked peptide may have certain advantages in that the disulfide bond can enhance structural stability and improve the biological activity of a large number of bioactive peptides. However, in certain cases, this bond is unstable to the reducing agent. Persons of ordinary skill in the art will understand that disulfide can be easily substituted for simple copper coins. Illustrative examples of such substitutions include, but are not limited to, thioether, dithioether, selenoether, diselenide, triazole, lactam, alkane and alkene groups. Thus, in certain embodiments of any of the peptide inhibitors described herein, one, two or more of the cysteine residues may be present, for example, as set forth below, or in any of the foregoing, Thioether, dithioether, selenoether, diselenide, triazole, lactam, alkane or alkene group. In certain embodiments, two of the substituted groups cyclize one or both of the peptide inhibitor or its monomer subunits by forming a bond (e.g., an intramolecular bond).

In certain embodiments, a peptide inhibitor of the invention is administered to a subject, for example, one of Tables 3a-3h, 4a, 4b, 5a-5c, 6, 7, 8, 9, 10, 11, 12, 13, Or comprises the amino acid sequence set forth in SEQ ID NO. In certain embodiments, a peptide inhibitor of the invention is administered to a subject, for example, one of Tables 3a-3h, 4a, 4b, 5a-5c, 6, 7, 8, 9, 10, 11, 12, 13, As shown in FIG.

In certain embodiments, the invention comprises a peptide inhibitor comprising a core consensus sequence selected from one of the following (presented in C-terminal direction at the N-terminus):

X ₁ X ₂ X ₂ WX ₂ X ₁ X ₂ W;

X ₁ X ₂ X ₂ WX ₂ X ₁ X ₂ (1-Nal);

X ₁ X ₂ X ₂ WX ₂ X ₁ X ₂ (2-Nal);

X ₁ X ₂ X ₂ WX ₂ X ₁ YW;

X ₁ X ₂ X ₂ WX ₂ X ₁ Y (1-Nal);

X ₁ X ₂ X ₂ WX ₂ X ₁ Y (2-Nal);

X ₁ X ₂ X ₂ WX ₂ X ₁ X ₂ X ₂ ;

_{X 1 X 2 X 2 WX 2} X 1 X 2 X 2 X 2 X 2 X 2 - [(D) Lys];

X ₁ X ₂ X ₂ WX ₂ X ₁ X ₃ X ₂ ;

X ₁ X ₂ X ₂ WX ₂ X ₁ X ₃ (1-Nal); And

X ₁ X ₂ X ₂ WX ₂ X ₁ X ₃ (2-Nal)

Wherein W is tryptophan, Y is tyrosine, the two X &lt; 1 &gt; residues are amino acids or other chemical moieties, each capable of forming an intramolecular bond with one another; Each X2 is independently selected from, for example, all amino acids including natural amino acids, L-amino acids, D-amino acids, non-natural amino acids, and unnatural amino acids; X3 is any amino acid. In certain embodiments, X3 is Phe, Phe analogs (e. G., Phe [4- (2-aminoethoxy) or Phe (4-CONH ₂₎₎ is, Tyr, or Tyr analogs (e. G., Tyr (Me)) . In certain embodiments, each Xl is selected from Cys, Pen, and Abu. In certain embodiments, each Xl is Cys. In certain embodiments, each Xl is a Pen. In certain embodiments, one X1 is Cys and the other X1 is Abu. In certain embodiments, the N-terminus Xl is Abu and the C-terminus Xl is Cys. In certain embodiments, the N-terminus Xl is Cys and the C-terminus Xl is Abu. In certain embodiments, the residues between the two Xl residues are Gln, Thr, Trp, and Gln. In certain embodiments, each Xl is selected from Cys, Pen and Abu; And X3 are Phe, Phe analogues such as Phe [4- (2-aminoethoxy)] or Phe (4-carbomide), Tyr, or Tyr analogs such as Tyr (Me). In certain embodiments, X3 is a Phe analog.

In certain embodiments, a peptide inhibitor of the invention comprises any of the following consensus sequences, wherein X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14 And X15 are defined as set forth in any of the various sequence or peptide inhibitors described herein:

X1-X2-X3-Pen-X5-X6-W-X8-Pen-X10-X11-X12-X13-X14-X15;

Pen-X5-X6-W-Q-Pen;

Pen-X5-X6-W-X8-Pen;

Pen-X5-X6-W-X8-Pen- [Phe (4-CONH2)];

Pen-X5-X6-W-X8-Pen- [Phe [4- (2-aminoethoxy)]];

X1-X2-X3-Abu-X5-X6-W-X8-C-X9-X10-X11-X12-X13-X14-X15;

Abu-X5-X6-W-Q-C;

Abu-X5-X6-W-X8-C;

Abu-X5-X6-W-X8-C- [Phe (4-CONH2)]; or

Abu-X5-X6-W-X8-C- [Phe [4- (2-aminoethoxy)]]].

In certain embodiments of any of the peptide inhibitors or monomer subunits, X7 and X11 are both W. In certain embodiments of any of the peptide inhibitors, X7 and X11 are both W and X10 is Y. In certain embodiments, X7 and X11 are both W and X10 is Phe [4- (2-aminoethoxy)] or Phe (4-OMe).

In certain embodiments of any of the peptide inhibitors or monomer subunits, X7 and X11 are not both W.

In certain embodiments of the peptide inhibitors of SEQ ID NO: I, X4 and X9 are each Pen and the intramolecular bond is a disulfide bond.

In certain embodiments, the peptide inhibitors of the present invention comprise, or alternatively consist of, the amino acid sequences set forth in any of the tables, sequence listings, or accompanying figures herein.

In certain embodiments of any of the peptide inhibitors described herein comprising an intramolecular bond, e.g., two amino acid residues joined by a disulfide bond, such as a Pen residue, two amino acid residues participating in the intramolecular bond One or both of which are not located at the N-terminal or C-terminal position of the peptide inhibitor. In certain embodiments, neither of the two amino acid residues involved in intramolecular binding, e.g., Pen, is located at the N-terminal or C-terminal position of the peptide inhibitor. In other words, in certain embodiments, at least one, or both, of the two amino acid residues that participate in the intramolecular bond, e.g., Pen, are internal amino acid residues of the peptide inhibitor. In certain embodiments, neither of the two amino acid residues involved in intramolecular binding, e.g., Pen, is located at the C-terminal position of the peptide inhibitor.

In some embodiments wherein the peptide of the invention is conjugated to an acidic compound, such as isovaleric acid, isobutyric acid, valeric acid, etc., the presence of said conjugate is referred to as the acidic form. Thus, for example, isobaryloyl- [Pen] -QTWQ [Pen] - [Phe (4-OMe)] - [2-Nal] - [a- MeLys] Instead of specifying conjugation of isovaleric acid to a peptide by mentioning isovaleroyl, such as - [Lys (Ac)] - NG-NH ₂ , in some embodiments, the present application is directed to isovaleric acid- [Pen] -QTWQ [Pen] - refers to the bonding as _{NG-NH 2 - [Phe (} 4-OMe)] - [2-Nal] - [a-MeLys] - [Lys (Ac)].

The invention further includes a peptide inhibitor that selectively binds to an epitope or binding domain that is present within amino acid residues 230-349 of human IL-23R protein. In certain embodiments, the peptide inhibitor binds to human IL-23R but not to murine IL-23R. In certain embodiments, the peptide inhibitor also binds to rat IL-23R.

In certain embodiments of the peptide inhibitors of SEQ ID NO: I, X4 is Abu; X9 is Cys, Pen, Homo cys, and the intramolecular bond is a thioether bond.

In certain embodiments of formula I, X4 is Cys, Pen, hCys, D-Pen, D-Cys or D-hCys; X9 is Abu; The intramolecular bond is a thioether bond.

In certain embodiments, the peptide inhibitor does not include the compounds disclosed in PCT Application No. PCT / US2014 / 030352 or PCT Application No. PCT / US2015 / 038370.

Pen-Pen Disulfide  Exemplary peptide inhibitors comprising binding

In certain embodiments, the invention includes a peptide inhibitor of the interleukin-23 receptor, or a pharmaceutically acceptable salt or solvate thereof, wherein the peptide inhibitor has the structure of Formula II:

R ¹ -XR ² (II)

Wherein R ¹ is selected from the group consisting of a bond, a hydrogen, a C 1 -C 6 alkyl, a C 6 -C 12 aryl, a C 6 -C 12 aryl, a C 1 -C 6 alkyl, a C 1 -C 20 alkanoyl, an alkylsulfonate, an acid, -Glu or pGlu, and a PEGylated version of any of the foregoing (e.g., 200 Da to 60,000 Da) alone or as a spacer thereof;

R ² is a bond, OH or NH ₂ ;

X is an amino acid sequence consisting of 8 to 20 amino acids or 8 to 35 amino acids.

In certain embodiments of the peptide inhibitor of SEQ ID NO: II, X comprises, or alternatively consists of, the sequence of SEQ ID &lt; RTI ID = 0.0 &

(IIa): X1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12-X13-

In this formula,

X1 is absent or is any amino acid;

X2 is absent, or is any amino acid;

X3 is absent or is any amino acid;

X4 is Pen, Cys or Homo-Cys;

X5 is any amino acid;

X6 is any amino acid;

X7 is Trp, Bip, Gln, His, Glu (Bzl), 4- benzyl alanine, Tic, Phe [4- (2- amino-ethoxy)], Phe (3,4-Cl 2), Phe (4- OMe), 5- hydroxy -Trp, 6- chloro -Trp, N-MeTrp, α- MeTrp, 1,2,3,4- tetrahydro-Nord _{hareuman, Phe (4-CO 2 H} ), Phe _{(4-CONH 2), Phe} (3,4- _{dimethoxy), Phe (4-CF 3} ), Phe (4-tBu), ββ-diPheAla, Glu, Gly, Ile, Asn, Pro, Arg, Thr , or Octgly, or the corresponding? -Methylamino form of any of the foregoing;

X8 is any amino acid;

X9 is Pen, Cys or hCys;

X10 is selected from the group consisting of 1-Nal, 2-Nal, Aic, Bip, (D) Cys, Cha, DMT, (D) Tyr, Glu, Phe, His, Trp, Thr, Tic, Tyr, Phe Tyr analogue or analogues _{(optionally, Phe (3,4-F 2)} , Phe (3,4-Cl 2), F (3-Me), Phe [4- ( 2-aminoethoxy)], Phe [4- (2- (acetyl-amino-ethoxy)], Phe (4-Br ), Phe (4-CONH 2), Phe (4-Cl), Phe (4-CN), Phe (4- guanidyl dino), Phe (4-Me) , Phe (4-NH 2), Phe (4-N 3), Phe (4-OMe), or Phe (4-OBzl)), or wherein in any of the equivalent to what methyl amino acid form;

X11 is 2-Nal, 1-Nal, 2,4- dimethyl-Phe, Bip, Phe (3,4- Cl 2), Phe (3,4-F 2), Phe (4-CO 2 H), βhPhe ( 4-F), α-Me -Trp, 4- _{phenyl-cyclohexyl, Phe (4-CF 3)} , α-MePhe, βhNal, βhPhe, βhTyr, βhTrp, Nva (5- phenyl), Phe, His, hPhe, (4-OMe), Phe (4-Me), Trp (2,5,7-tri-tert-butyl), Phe ), Phe (4-tBu), Phe (4-guanidino, Phe (4-OBzl), Octgly, Glu (Bzl), 4-phenylbenzylalanine, Phe [4- 5-hydroxy--Trp, 6- chloro -Trp, N-MeTrp, 1,2,3,4- tetrahydro-Nord _{hareuman, Phe (4-CONH 2)} , Phe (3,4-OMe 2) Phe ( _{2,3-Cl 2), Phe (} 2,3-F 2), Phe (4-F), 4- phenyl-cyclohexyl alanine or Bip, or the one of any of the corresponding methyl α- amino acid to form a;

(D) Ala, (D) Asn (A), Ala (A), Ala, Asp, (D) Phe, (D) Thr, 3-Pal, Aib,? -Ala,? HGlu,? HAla,? HLeu,? HVal,? -Spiro -pip, Cha, Chg, Asp , Dab, Dap,? -Diethyl Gly, Glu, Phe, hLeu, hArg, hLeu, Ile, Lys, Leu, Asn, N-MeLeu, N-MeArg, Ogl, Orn, Pro, Gln, Or Tle, or the corresponding? -Methylamino form of any of the foregoing;

X13 is selected from the group consisting of Lys (Ac), (D) Asn, (D) Leu, (D) Thr, (D) Phe, Ala, Aib,? -MeLeu,? -Ala,? HGlu,? HAla,? HLeu, Gly, Phe, hLeu, Lys, Leu, Asn, Ogl, Pro, Gln, Asp, Arg, Ser, Spiro, Phe, Cha, Chg, Asp, Lys, Arg, Orn, Dab, Dap, -pip, Thr, Tba, Tlc, Val or Tyr, or the corresponding? -methylamino form of any of the foregoing;

X14 is selected from the group consisting of Asn, Glu, Phe, Gly, His, Lys, Leu, Met, Asn, Pro, Gln, Arg, Ser, Thr, Tic or Tyr, Lys Methyl amino acid form;

Asp, Asn, (D) Leu, (D) Phe, (D) Thr, Ala, AEA, Asp, Glu, Phe, Gly, Lys, Leu, Pro, Gln, Arg or Ser, [beta] -Ala, Arg or the corresponding [alpha] -methyl amino acid forms of any of the foregoing;

X16 is absent or is the corresponding? -Methylamino form of any of Gly, Ala, Asp, Ser, Pro, Asn or Thr, or any of the foregoing;

X17 is absent or is the corresponding? -Methylamino form of Glu, Ser, Gly or Gln, or any of the foregoing;

X18 is absent, or is any amino acid;

X19 is absent or is any amino acid;

X20 is absent or is any amino acid.

In certain embodiments of IIa: X10 is selected from 1-Nal, 2-Nal, Aic, Bip, (D) Cys, Cha, DMT, (D) Tyr, Glu, Phe, His, Trp, Thr, Tic, - pyridyl Ala, Octgly, Phe analogs or Tyr analogues, or the corresponding [alpha] -methyl amino acid forms of any of the foregoing; X11 is 2-Nal, 1-Nal, 2,4- dimethyl-Phe, Bip, Phe (3,4- Cl 2), Phe (3,4-F 2), Phe (4-CO 2 H), βhPhe ( 4-F), α-Me -Trp, 4- _{phenyl-cyclohexyl, Phe (4-CF 3)} , α-MePhe, βhNal, βhPhe, βhTyr, βhTrp, Nva (5- phenyl), Phe, His, hPhe, (4-OMe), Phe (4-Me), Trp (2,5,7-tri-tert-butyl), Phe ), Phe (4-tBu), Phe (4-guanidino, Phe (4-OBzl), Octgly, Glu (Bzl), 4-phenylbenzylalanine, Phe [4- 5-hydroxy--Trp, 6- chloro -Trp, N-MeTrp, 1,2,3,4- tetrahydro-Nord _{hareuman, Phe (4-CONH 2)} , Phe (3,4- dimethoxy), Phe _{(2,3-Cl 2), Phe} (2,3-F 2), Phe (4-F), 4- phenyl-cyclohexyl alanine or Bip, or the one of any of the corresponding methyl α- amino acid to form a; (D) Asp, (D) Asp, (D) Phe, (D) Thr, 3-MeLys, Asp, Dab, Dap,? -Diethyl Gly, Glu, Phe, hLeu, hArg, hLeu, Ile,? -Hal,? HAe,? HLeu,? HVal,? -Spiro-pip, Cha, Chg, Asp, Dab, Dap, Lys, Le (Ac), &lt; / RTI &gt; or &lt; RTI ID = 0.0 &gt; (D) Asn, (D) Leu, (D) Thr, (D) Phe, Ala, Aib,? -MeLeu,? -Ala,? HGlu,? HAla,? HLeu,? Asp, Lys, Arg, Orn, Dab, Dap,? -Diethyl Gly, Glu, Phe, hLeu, Lys, Leu, Asn, Ogl, Pro, Gln, Asp, Arg, Ser, Spiroip, Thr, Tba, Tlc, Val or Tyr, or the corresponding? -Methylamino form of any of the foregoing; X14 is a corresponding? -Methyl amino acid form of any of the foregoing, or Asn, Glu, Phe, Gly, His, Lys, Leu, Met, Asn, Pro, Gln, Arg, Ser, Thr, Tic or Tyr; Asp, Asn, (D) Leu, (D) Phe, (D) Thr, Ala, AEA, Asp, Glu, Phe, Gly, Lys, Leu, Pro, Gln, Arg or Ser, or the corresponding [alpha] -methyl amino acid forms of any of the foregoing.

In certain embodiments, X3 is present. In certain embodiments, X3 is Glu, (D) Glu, Arg, (D) Arg, Phe, (D) Phe, 2-Nal, Thr, Leu, (D) Gln. In certain embodiments, X3 is (D) Arg or (D) Phe. In certain embodiments, X1 and X2 are absent and X3 is present.

In certain embodiments, X5 is selected from the group consisting of Gln, Ala, Cit, Asp, Dab, Dap, Cit Glu, Phe, Gly, His, hCys, Lys, Leu, Met, Asn, N-Me- Me-Lys,? -Me-Lys,? -Me-Orn, N-Me-Gln, N-Me-Arg,? -MeSer, Orn, Pro, Arg, Ser, Thr or Val. In certain embodiments, X5 is selected from the group consisting of Gln, Ala, Cit, Asp, Dab, Dap, Glu, Phe, Gly, His, hCys, Lys, Leu, Met, Asn, N-Me- -Me-Lys,? Me-Lys,? Me-Orn, N-Me-Gln, N-Me-Arg, Orn, Pro, Arg, Ser, Thr or Val. In certain embodiments, X5 is Gln or Asn.

In certain embodiments, X6 is Thr, Asp, Glu, Phe, Asn, Pro, Arg, or Ser.

In certain embodiments, X7 is Trp.

In certain embodiments, X8 is Gln, Glu, Phe, Lys, Asn, Pro, Arg, Val, Thr, or Trp.

In certain embodiments, XlO is a Tyr analog or a Phe analog. In certain embodiments, X10 is a Phe analog.

X10 is Phe in analogue certain embodiments, X10 is hPhe, Phe (4-OMe) , α-Me-Phe, hPhe (3,4- _{dimethoxy), Phe (4-CONH 2} ), Phe (4- fluorophenyl City), Phe (4- iguana dino), Phe (4-tBu) , Phe (4-CN), Phe (4-Br), Phe (4-OBzl), Phe (4-NH 2), Phe ( 4-F), Phe (3,5 DiF), Phe (CH 2 CO 2 H), Phe ( penta -F), Phe (3,4-Cl 2), Phe (4-CF 3), ββ-diPheAla , Phe (4-N ₃ ) and Phe [4- (2-aminoethoxy)]. In certain embodiments, X10 is Phe (4-OMe) or Phe [4- (2-aminoethoxy)]. In certain embodiments, X10 is Phe (4-OMe), Phe (4-CONH 2) , or Phe [4- (2-aminoethoxy)]. X10 is Phe in analogue certain embodiments, X10 is hPhe, Phe (4-OMe) , α-Me-Phe, hPhe (3,4- _{dimethoxy), Phe (4-CONH 2} ), Phe (4- fluorophenyl City), Phe (4- iguana dino), Phe (4-tBu) , Phe (4-CN), Phe (4-Br), Phe (4-OBzl), Phe (4-NH 2), Phe ( 4-F), Phe (3,5 DiF), Phe (CH 2 CO 2 H), Phe ( penta -F), Phe (3,4-Cl 2), Phe (4-CF 3), ββ-diPheAla , Phe (4-N ₃ ) and Phe [4- (2-aminoethoxy)]. In certain embodiments, X10 is Phe (4-OMe).

X10 is a Tyr analogue chain In certain embodiments, X10 is from hTyr, α-MeTyr, N- MeTyr, Tyr (3-tBu), Phe (4-CONH 2), Phe [4- ( 2-aminoethoxy)], and bhTyr Is selected. X10 is a Tyr analogue chain In certain embodiments, XlO is selected from hTyr, alpha-MeTyr, N-Me-Tyr, Tyr (3-tBu), and bhTyr.

In certain embodiments, X10 is Tyr, Phe (4-OMe) , Phe [4- (2- amino-ethoxy)], Phe (4-CONH 2), or 2-Nal. In certain embodiments, X10 is Phe (4-OMe) or Phe [4- (2-aminoethoxy)]. In certain embodiments, XlO is not Tyr.

In certain embodiments, X11 is a Trp analog. In certain embodiments, X11 is 2-Nal or 1-Nal. In certain embodiments, X11 is 2-Nal.

In certain embodiments, X12 is Aib, [alpha] -MeLys or [alpha] -MeLeu.

In certain embodiments of the peptide inhibitor of SEQ ID NO: II, one or both of X4 or X9 is Pen. In certain embodiments, X4 and X9 are both Pen.

In certain embodiments, the peptide inhibitor of SEQ ID NO: II is a cyclized one. In certain embodiments, the peptide inhibitor of SEQ ID &lt; RTI ID = 0.0 &gt; Il &lt; / RTI &gt; is cyclized through an intramolecular bond between X4 and X9. In certain embodiments, the intramolecular bond is a disulfide bond. In certain embodiments, both X4 and X9 are Pen.

In certain embodiments, the peptide inhibitor of SEQ ID NO: II is linear or non-pecylated. In certain embodiments of the linear peptide inhibitor of SEQ ID NO: I, X4 and / or X9 is any amino acid.

In certain embodiments of the peptide inhibitor of SEQ ID NO: II, no more than one, two or more, or all three of X1, X2, and X3 are present. In certain embodiments, X1 is absent. In certain embodiments, X1 and X2 are absent. In certain embodiments, X1, X2, and X3 are absent.

In certain embodiments of the peptide inhibitors of SEQ ID NO: II, no more than one, two or more, three or more, four or more of X16, X17, X18, X19 and X20 are present. In certain embodiments of the peptide inhibitors of SEQ ID NO: I, no more than one, two or more, three or more of X17, X18, X19 and X20 are present. In certain embodiments, no more than one, two or more, or all three of X17, X19, and X20 are present. In certain embodiments, at least one of Xl, X2, and X3 is absent; At least one, at least two, at least three, or four of X17, X18, X19 and X20 are not present.

In certain embodiments of the peptide inhibitor of SEQ ID NO: II, X18 is (D) -Lys. In certain embodiments, X18 is absent (D) -Lys and X17.

In certain embodiments of the peptide inhibitors of SEQ ID NO: II, the peptide inhibitor comprises one or more, two or more, three or more of the following features: X5 is Asn, Arg or Gln; X6 is Thr; X7 is Trp; X8 is Gln. In certain embodiments of the peptide inhibitor of SEQ ID &lt; RTI ID = 0.0 &gt; I &lt; / RTI &gt; X5 is Gln, Asn or Arg; X6 is Thr; X7 is Trp, 5-hydroxy-Trp, 6-chloro-Trp, N-MeTrp, alpha-Me-Trp, or 1,2,3,4-tetrahydro-norharman; X8 is Gln; X9 is a Pen. In certain embodiments, X5 is Gln. In certain embodiments, X1, X2, and X3 are absent. In certain embodiments, X4 and X9 are both Pen.

In certain embodiments of the peptide inhibitors of SEQ ID NO: II, the peptide inhibitor comprises one or more, two or more, three or more, four or more, five or more, six or more of the following features: Tyr, Phe analog, Tyr analog or 2-Nal; X11 is Trp, 5-hydroxy-Trp, 6-chloro-Trp, N-MeTrp, alpha-Me-Trp, 1,2,3,4-tetrahydro-norharmann, 2-Nal or 1-Nal; X12 is Aib,? -MeLys,? -MeOrn and? -MeLeu; X13 is Lys, Glu or Lys (Ac); X14 is Phe or Asn; X15 is GIy, Ser or Ala; And X16 are absent, or AEA. In certain embodiments, X10 is Tyr, Phe (4-OMe) , Phe [4- (2- _{amino-ethoxy)], Phe (CONH 2)} , or 2-Nal. In certain embodiments, X11 is 2-Nal or 1-Nal. In certain embodiments, XlO is not Tyr. In certain embodiments, X1, X2, and X3 are absent. In certain embodiments, X4 and X9 are both Pen.

In certain embodiments of the peptide inhibitors of SEQ ID NO: II, the peptide inhibitor may comprise one or more, two or more, three or more, four or more, five or more, six or more, seven or more, 9 or more, 10 or more, or 11: X5 is Arg or Gln; X6 is Thr; X7 is Trp; X8 is Gln; X10 is a Phe analog; X11 is Trp, 2-Nal or 1-Nal; X12 is Aib,? -MeLys or? -MeOrn; X13 is Lys, Glu or Lys (Ac); X14 is Asn; X15 is GIy, Ser or Ala; X16 is absent, or AEA. In certain embodiments, X10 is Phe (4-OMe) or Phe [4- (2-aminoethoxy)]. In certain embodiments, X11 is 2-Nal or 1-Nal. In certain embodiments, X1, X2, and X3 are absent. In certain embodiments, X4 and X9 are both Pen.

In certain embodiments of the peptide inhibitor of SEQ ID NO: II, the peptide is cyclized via X4 and X9; X4 and X9 are Pen; X5 is Gln; X6 is Thr; X7 is Trp; X8 is Gln; X10 is Tyr, Phe analog or 2-Nal; X11 is Trp, 2-Nal or 1-Nal; X12 is Arg,? -MeLys,? -MeOrn, or? -MeLeu; X13 is Lys, Glu or Lys (Ac); X14 is Phe or Asn; X15 is GIy, Ser or Ala; X16 does not exist. In certain embodiments, X10 is Tyr, Phe (4-OMe), Phe [4- (2-aminoethoxy)], Phe (4-OMe), or 2-Nal. In certain embodiments, X10 is Phe (4-OMe). In certain embodiments, XlO is not Tyr. In certain embodiments, X11 is 2-Nal or 1-Nal. In certain embodiments, X1, X2, and X3 are absent.

In certain embodiments of the peptide inhibitor of SEQ ID NO: II, the peptide is cyclized via X4 and X9; X4 and X9 are Pen; X5 is Gln; X6 is Thr; X7 is Trp; X8 is Gln; X10 is Tyr, Phe (4-OMe) or 2-Nal; X11 is Trp, 2-Nal or 1-Nal; X12 is Arg,? -MeLys or? -MeOrn; X13 is Lys, Glu or Lys (Ac); X14 is Phe or Asn; X15 is GIy; X16 does not exist. In certain embodiments, X10 is Phe (4-OMe). In certain embodiments, X11 is 2-Nal or 1-Nal. In certain embodiments, X1, X2, and X3 are absent.

In certain embodiments of the peptide inhibitor of SEQ ID NO: II, the peptide is cyclized via X4 and X9; X4 and X9 are Pen; X5 is Gln; X6 is Thr; X7 is Trp; X8 is Gln; X10 is Phe (4-OMe) or Phe [4- (2-aminoethoxy)]; X11 is Trp, 2-Nal or 1-Nal; X12 is? -MeLys,? -MeOrn, or? -MeLeu; X13 is Lys, Glu or Lys (Ac); X14 is Asn; X15 is GIy, Ser or Ala; X16 does not exist. In certain embodiments, X10 is Phe (4-OMe). In certain embodiments, X11 is 2-Nal or 1-Nal. In certain embodiments, X1, X2, and X3 are absent.

In certain embodiments of the peptide inhibitor of SEQ ID NO: II, X10 is not Tyr.

In certain embodiments, the invention includes an optionally cyclized one comprising, or consisting of, or having the core sequence of SEQ ID &lt; RTI ID = 0.0 &gt; IIb &lt; / RTI &gt; , Optionally 8 to 35, 8 to 20, 8 to 16 or 8 to 12 amino acids in length.

Pen-Xaa5-Xaa6-Trp-Xaa8-Pen-Xaa10 - [(2-Nal)] (IIb)

Wherein Xaa5, Xaa6 and Xaa8 are any amino acid residues; And Xaa10 is a Phe analog. In certain embodiments, X10 is a α-Me-Phe, Phe ( 4-OMe), Phe (4-OBzl), Phe (4-OMe), Phe (4-CONH 2), Phe (3,4-Cl 2 ), Phe (4-tBu) , Phe (4-NH 2), Phe (4-Br), Phe (4-CN), Phe (4-CO 2 H), Phe [4- (2- amino-ethoxy )] Or Phe (4-guanadino). In certain embodiments, Xaa10 is Phe (4-OMe) or Phe [4- (2-aminoethoxy)]. In one embodiment, Xaa10 is Phe (4-OMe). In certain embodiments, the peptide is cyclized via an intramolecular bond between the Pen of Xaa4 and the Pen of Xaa9. In certain embodiments, the peptide is a peptide inhibitor of SEQ ID NO: II, wherein, in certain embodiments, X1, X2 and X3 are absent. In certain embodiments, the peptides inhibit the binding of IL-23 to IL-23R. In certain embodiments, the peptide of SEQ ID &lt; RTI ID = 0.0 &gt; IIb &lt; / RTI &gt; further comprises an amino acid bound to the N-terminal Pen residue. (D) Glu, Arg, (D) Arg, Phe, (D) Phe, 2-Nal, Thr, Leu, or (D) Gln in certain embodiments. In certain embodiments, this is (D) Arg or (D) Phe.

In certain embodiments, the invention includes an optionally cyclized one comprising, or consisting of, or having the core sequence of the following sequence formula IIc, which inhibits the binding of IL-23 to IL-23R , Optionally 8 to 35, 8 to 20, 8 to 16 or 8 to 12 amino acids in length.

Pen-Xaa5-Xaa6-Trp-Xaa8-Pen-Xaa10 - [(2-Nal)] (IIc)

Wherein Xaa5, Xaa6 and Xaa8 are any amino acid residues; Xaa10 is Tyr, Phe analogue,? -Me-Tyr,? -Me-Trp or 2-Nal. In certain embodiments, XlO is selected from the group consisting of Tyr, Phe (4-OMe), Phe [4- (2-aminoethoxy)], alpha-Me-Tyr, alpha-Me- to be. In certain embodiments, Xaa10 is Tyr, Phe (4-OMe) , Phe (CONH 2), Phe [4- (2- amino-ethoxy)] or a 2-Nal. In certain embodiments, Xaa10 is Tyr, Phe (4-OMe), Phe [4- (2-aminoethoxy)], or 2-Nal. In certain embodiments, Xaa10 is Phe (4-OMe) or Phe [4- (2-aminoethoxy)]. In one embodiment, Xaa10 is Phe [4- (2-aminoethoxy) or Phe (CONH _2). In certain embodiments, Xaa10 is Phe (4-OMe) or Phe [4- (2-aminoethoxy)]. In one embodiment, Xaa10 is Phe [4- (2-aminoethoxy)]. In certain embodiments, Xaa10 is not Tyr. In certain embodiments, the peptide is cyclized through an intramolecular bond between the Pen of Xaa4 and the Pen of Xaa9. In certain embodiments, the peptide is a peptide inhibitor of SEQ ID NO: II, wherein, in certain embodiments, X1, X2 and X3 are absent. In certain embodiments, the peptides inhibit the binding of IL-23 to IL-23R. In certain embodiments, the peptide of SEQ ID &lt; RTI ID = 0.0 &gt; IIc &lt; / RTI &gt; further comprises an amino acid bonded to the N-terminal Pen residue. (D) Glu, Arg, (D) Arg, Phe, (D) Phe, 2-Nal, Thr, Leu, or (D) Gln in certain embodiments. In certain embodiments, this is (D) Arg or (D) Phe.

In certain embodiments, the present invention provides a polynucleotide comprising, optionally, 8 to 35, 8 to 20, 8 to 16, or 10, RTI ID = 0.0 &gt; 8 &lt; / RTI &gt; to 12 amino acids in length:

Pen-Xaa5-Xaa6-Trp-Xaa8-Pen-Phe [4- (2-aminoethoxy)] - [2-

Wherein Xaa5, Xaa6 and Xaa8 are any amino acid residues. In certain embodiments, the peptide comprises a disulfide bond between Xaa4 and Xaa9. In certain embodiments, the peptide is a peptide inhibitor of SEQ ID NO: I, wherein, in certain embodiments, X1, X2, and X3 are absent. In certain embodiments, the peptides inhibit the binding of IL-23 to IL-23R. In certain embodiments, the peptide of SEQ ID &lt; RTI ID = 0.0 &gt; IId &lt; / RTI &gt; further comprises an amino acid bonded to the N-terminal Pen residue. (D) Glu, Arg, (D) Arg, Phe, (D) Phe, 2-Nal, Thr, Leu, or (D) Gln in certain embodiments. In certain embodiments, this is (D) Arg or (D) Phe.

In certain embodiments of the peptide inhibitors of Formula II, the peptide inhibitor has a structure as set forth in any of Tables 2, 3, 4a, 4b, 8, 11 or 15, or as Tables 2, 3, 4a, 4b, 8, 11 Or &lt; RTI ID = 0.0 &gt; 15. &Lt; / RTI &gt;

[Table 2]

[Table 3]

Exemplary peptide inhibitors comprising thioether linkages

In certain embodiments, the invention includes a peptide inhibitor of an interleukin-23 receptor, or a pharmaceutically acceptable salt or solvate thereof, wherein the peptide inhibitor has a structure of Formula III:

R ¹ -XR ² (III)

Wherein R ¹ is selected from the group consisting of a bond, a hydrogen, a C 1 -C 6 alkyl, a C 6 -C 12 aryl, a C 6 -C 12 aryl, a C 1 -C 6 alkyl, a C 1 -C 20 alkanoyl, an alkylsulfonate, an acid, -Glu or pGlu, and a PEGylated version of any of the foregoing (e.g., 200 Da to 60,000 Da) alone or as a spacer thereof;

R ² is a bond, OH or NH ₂ ;

X is an amino acid sequence consisting of 8 to 20 amino acids or 8 to 35 amino acids.

In certain embodiments of the peptide inhibitor of SEQ ID NO: &lt; RTI ID = 0.0 &gt; III, &lt; / RTI &gt; X comprises or consists of a sequence of the following sequence IIIa:

(XII): X1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12-

In this formula,

X1 is absent or is any amino acid;

X2 is absent, or is any amino acid;

X3 is absent or is any amino acid;

X4 is Abu, Pen, or Cys;

X5 is any amino acid;

X6 is any amino acid;

X7 is Trp, Bip, Gln, His, Glu (Bzl), 4- benzyl alanine, Tic, Phe [4- (2- amino-ethoxy)], Phe (3,4-Cl 2), Phe (4- OMe), 5- hydroxy -Trp, 6- chloro -Trp, N-MeTrp, α- MeTrp, 1,2,3,4- tetrahydro-Nord _{hareuman, Phe (4-CO 2 H} ), Phe (4 _{-CONH 2), Phe (3,4- (} OCH 3) 2), Phe (4-CF 3), ββ-diPheAla, Phe (4-tBu), Glu, Gly, Ile, Asn, Pro, Arg, Thr Or Octgly, or the corresponding? -Methylamino form of any of the foregoing;

X8 is any amino acid;

X9 is Abu, Pen, or Cys;

X10 is selected from the group consisting of 1-Nal, 2-Nal, Aic, Bip, (D) Cys, Cha, DMT, (D) Tyr, Glu, Phe, His, Trp, Thr, Tic, Tyr, analogs or analogs Tyr _{(optionally, Phe (3,4-F 2)} , Phe (3,4-Cl 2), F (3-Me), Phe [4- ( 2-aminoethoxy)], Phe [ 4- (2- (acetyl-amino-ethoxy)], Phe (4-Br ), Phe (4-CONH 2), Phe (4-Cl), Phe (4-CN), Phe (4- guanidino ), Phe (4-Me) , Phe (4-NH 2), Phe (4-N 3), Phe (4-OMe), Phe (4-OBzl)), or of any of the corresponding α- Methyl amino acid form;

X11 is selected from the group consisting of 2-Nal, 1-Nal, 2,4-dimethyl Phe, Bip, 4-phenylcyclohexyl, Glu (Bzl), 4-phenylbenzylalanine, Tic, Phe [4- (2-aminoethoxy) _{, Phe (3,4-Cl 2)} , Phe (3,4-F 2), βhPhe (4-F), Phe (4-OMe), 5- hydroxy -Trp, 6- chloro -Trp, N- MeTrp,? -MeTrp, 1,2,3,4-tetrahydro-norharmane, Phe (4-CO ₂ H), Phe (4-CONH ₂ ), Phe (3,4-dimethoxy) _{-CF 3), Phe (2,3-} Cl 2), Phe (3,4-Cl 2), Phe (2,3-F 2), Phe (4-F), 4- phenyl-cyclohexyl alanine, α Phe, His, hPhe, Tqa, Trp, Tyr, Phe (4-Me), Trp (2,5,7-tri-tert-butylphenyl) Butyl), Phe (4-O allyl), Tyr (3-tBu), Phe (4-tBu), Phe (4- guanidino), Phe The corresponding? -Methylamino form;

(D) Asp, (D) Asp, (D) Phe, (D) Thr, 3-MeLys, Asp, Dab, Dap,? -Diethyl Gly, Glu, Phe, hLeu, hArg, hLeu, Ile,? -Hal,? HAe,? HLeu,? HVal,? -Spiro-pip, Cha, Chg, Asp, Dab, Dap, Acv Acpc, Acbc, Acvc, Gln, Arg, Ser, Thr or Tle, amino-4-carboxy-tetrahydropyran (THP), Lys, Leu, Asn, N-MeLeu, N-MeArg, Ogl, Orn, Aib, or the corresponding? -Methylamino form of any of the foregoing;

X13 is selected from the group consisting of Lys Lys (Ac), (D) Asn, (D) Leu, (D) Thr, (D) Phe, Ala, Aib,? -MeLeu,? Ala,? HGlu,? HAla,? HLeu,? Pip, Cha, Chg, Asp, Arg, Orn, Dab, Dap, a-diethyl Gly, Glu, Phe, hLeu, Lys, Leu, Asn, Ogl, Pro, Gln, Asp, Arg, Ser, Thr, Tba, TIc, Val or Tyr, or the corresponding [alpha] -methyl amino acid forms of any of the foregoing;

X14 is selected from the group consisting of Asn, Glu, Phe, Gly, His, Lys, Lys (Ac), Leu, Met, Asn, Pro, Gln, Arg, Ser, Thr, Tic, Asp or Tyr, - methyl amino acid form;

Asp, Asn, (D) Leu, (D) Phe, (D) Thr, Ala, AEA, Asp, Glu, Phe, Gly, Lys, Leu, Pro, Gln, Arg,? -Ala, or Ser, or the corresponding? -Methylamino form of any of the foregoing;

X16 is absent or is the corresponding? -Methylamino form of any of Gly, Ala, Asp, Ser, Pro, Asn or Thr, or any of the foregoing;

X17 is absent or is the corresponding? -Methylamino form of Glu, Ser, Gly or Gln, or any of the foregoing;

X18 is absent, or is any amino acid;

X19 is absent or is any amino acid;

X20 is absent or is any amino acid.

In certain embodiments, X 14 is selected from the group consisting of Asn, Glu, Phe, Gly, His, Lys, Lys (Ac), Leu, Met, Asn, Pro, Gln, Arg, Ser, Thr, Tic, Methylamino &lt; / RTI &gt; acid form of any.

In certain embodiments of IIIa: X7 is selected from the group consisting of Trp, Bip, Gln, His, Glu (Bzl), 4-phenylbenzylalanine, Tic, Phe [4- (2-aminoethoxy)], Phe ₂ -Phe (4-OMe), 5-hydroxy-Trp, 6-chloro-Trp, N-MeTrp,? -MeTrp, 1,2,3,4-tetrahydro- _{2 H), Phe (4-} CONH 2), Phe (3,4- _{dimethoxy), Phe (4-CF 3} ), ββ-diPheAla, Phe (4-tBu), Glu, Gly, Ile, Asn, Pro , Arg, Thr or Octgly, or the corresponding [alpha] -methyl amino acid forms of any of the foregoing; X10 is selected from the group consisting of 1-Nal, 2-Nal, Aic, Bip, (D) Cys, Cha, DMT, (D) Tyr, Glu, Phe, His, Trp, Thr, Tic, Tyr, Analog or Tyr analog, or the corresponding? -Methyl amino acid form of any of the foregoing; X11 is selected from the group consisting of 2-Nal, 1-Nal, 2,4-dimethyl Phe, Bip, 4-phenylcyclohexyl, Glu (Bzl), 4-phenylbenzylalanine, Tic, Phe [4- (2-aminoethoxy) _{, Phe (3,4-Cl 2)} , Phe (3,4-F 2), βhPhe (4-F), Phe (4-OMe), 5- hydroxy -Trp, 6- chloro -Trp, N- MeTrp,? -MeTrp, 1,2,3,4-tetrahydro-norharmane, Phe (4-CO ₂ H), Phe (4-CONH ₂ ), Phe (3,4-dimethoxy) _{-CF 3), Phe (2,3-} Cl 2), Phe (2,3-F 2), Phe (4-F), 4- phenyl-cyclohexyl-alanine, α-MePhe, βhNal, βhPhe , βhTyr, βhTrp Phe (4-O-allyl), Bip, Nva (5-phenyl), Phe, His, hPhe, Tqa, Trp, Tyr, Phe , Tyr (3-tBu), Phe (4-tBu), Phe (4-guanidino), Phe (4-OBzl), or Octgly or the corresponding? -Methyl amino acid forms of any of the foregoing; (D) Asp, (D) Asp, (D) Phe, (D) Thr, 3-MeLys, Asp, Dab, Dap,? -Diethyl Gly, Glu, Phe, hLeu, hArg, hLeu, Ile,? -Hal,? HAe,? HLeu,? HVal,? -Spiro-pip, Cha, Chg, Asp, Dab, Dap, Lys, Leu, Asn, N-MeLeu, N-MeArg, Ogl, Orn, Pro, Gln, Arg, Ser, Thr or Tle or the corresponding? -Methylamino form of any of the foregoing; X13 is Lys (Ac), (D) Asn, (D) Leu, (D) Thr, (D) Phe, Ala, Aib,? -MeLeu,? Ala,? HGlu,? HAla,? HLeu,? HVal, , Cha, Chg, Asp, Arg, Orn, Dab, Dap,? -Diethyl Gly, Glu, Phe, hLeu, Lys, Leu, Asn, Ogl, Pro, Gln, Asp, Arg, Ser, , Tba, TIc, Val or Tyr, or the corresponding [alpha] -methyl amino acid forms of any of the foregoing; X14 is a corresponding? -Methyl amino acid form of any of the foregoing, or Asn, Glu, Phe, Gly, His, Lys, Leu, Met, Asn, Pro, Gln, Arg, Ser, Thr, Tic or Tyr; Asp, Asn, (D) Leu, (D) Phe, (D) Thr, Ala, AEA, Asp, Glu, Phe, Gly, Lys, Leu, Pro, Gln, Arg or Ser, or the corresponding [alpha] -methyl amino acid forms of any of the foregoing.

In certain embodiments, X3 is present. In certain embodiments, X3 is Glu, (D) Glu, Arg, (D) Arg, Phe, (D) Phe, 2-Nal, Thr, Leu or (D) Gln. In certain embodiments, this is (D) Arg or (D) Phe.

In certain embodiments, X5 is selected from Gln, Ala, Cys, Cit, Asp, Dab, Dap, Glu, Phe, Gly, His, hCys, Lys, Leu, Met, Asn, N-Me- -Me-Lys, N-Me-Gln, N-Me-Arg, Orn, Pro, Pen, Gln, Arg, Ser, Thr or Val.

In certain embodiments, X6 is Thr, Asp, Glu, Phe, Asn, Pro, Arg, Ser, or Thr.

In certain embodiments, X8 is Gln, Glu, Phe, Lys, Asn, Pro, Arg, Val, Thr, or Trp.

In certain embodiments, XlO is a Tyr analog or a Phe analog. In certain embodiments, X10 is Phe (4-OMe), Phe (CONH 2) or Phe [4- (2-aminoethoxy)]. In certain embodiments, XlO is a Tyr analog or a Phe analog. In certain embodiments, X10 is Phe (4-OMe) or Phe [4- (2-aminoethoxy)].

In certain embodiments X10 is Phe would analogue, X10 is hPhe, Phe (4-OMe) , α-MePhe, hPhe (3,4- _{dimethoxy), Phe (4-CONH 2} ), Phe (4-O -Bzl)), Phe (4- iguana dino), Phe (4-tBu) , Phe (4-CN), Phe (4-Br), Phe (4-NH 2), Phe (4-F), Phe (3,5 DiF), Phe ( CH 2 CO 2 H), Phe ( penta -F), Phe (3,4-Cl 2), Phe (4-CF3), ββ-diPheAla, Phe (4-N ₃ ) and Phe [4- (2-aminoethoxy)]. In certain embodiments, X10 is Phe [4- (2-aminoethoxy) or Phe (CONH _2). In certain embodiments, X10 is Phe [4- (2-aminoethoxy)].

In certain embodiments wherein XlO is a Tyr analogue, XlO is selected from hTyr, N-Me-Tyr, Tyr (3-tBu), Phe (4-OMe) and bhTyr. In certain embodiments, X10 is Phe (4-OMe).

In certain embodiments, X10 is Tyr, Phe (4-OMe) , Phe (4-OBzl), Phe (4-OMe), Phe (4-CONH 2), Phe (3,4-Cl 2), Phe ( 4-tBu), Phe (4-NH2), Phe (4-Br), Phe (4-CN), Phe Anadino). In certain embodiments, XlO is not Tyr

In certain embodiments, X11 is a Trp or Trp analog. In certain embodiments, X11 is 2-Nal or 1-Nal.

In certain embodiments, the peptide inhibitor of SEQ ID &lt; RTI ID = 0.0 &gt; III &lt; / RTI &gt; In certain embodiments, the peptide inhibitor is cyclized through an intramolecular bond between X4 and X9. In certain embodiments, the intramolecular bond is a thioether bond.

In certain embodiments, the peptide inhibitor of SEQ ID NO: III is linear or non-cyclized. In certain embodiments of the peptide inhibitor of linear sequence III, X4 and / or X9 is any amino acid.

In certain embodiments of the peptide inhibitors of SEQ ID NO: III, none, more than one, or all three of X1, X2, and X3 are absent. In certain embodiments, X1 is absent. In certain embodiments, X1 and X2 are absent. In certain embodiments, X1, X2, and X3 are absent.

In certain embodiments of the peptide inhibitors of SEQ ID NO: III, at least one, at least two, at least three, at least four, or all of X16, X17, X18, X19 and X20 are absent. In certain embodiments of the peptide inhibitors of SEQ ID NO: III, at least one, at least two, at least three, or both of X17, X18, X19 and X20 are absent. In certain embodiments, no more than one, two or more, or all three of X17, X19, and X20 are present. In certain embodiments, no more than one of X1, X2, and X3 is present; At least one, at least two, at least three, or four of X17, X18, X19 and X20 are not present.

In certain embodiments of the peptide inhibitors of SEQ ID NO: III, one of X4 or X9 is Abu and the other of X4 or X9 is not Abu. In certain embodiments, X4 is Abu and X9 is Cys.

In certain embodiments, the peptide inhibitor of SEQ ID NO: III comprises one or more, two or more, three or more of the following features: X5 is Arg or Gln; X6 is Thr; X7 is Trp; X8 is Gln. In certain embodiments, X5 is Gln, X6 is Thr, X7 is Trp, and X8 is Gln. In certain embodiments, X5 is Gln. In certain embodiments, X1, X2, and X3 are absent. In certain embodiments, X4 is Abu and X9 is Cys.

In certain embodiments, the peptide inhibitor of SEQ ID NO: III comprises one or more, two or more, three or more, four or more, five or more, six or more of the following features: X10 is Tyr or Phe analogs; X11 is Trp, 2-Nal, 1-Nal, Phe (4-O-allyl), Tyr (3-tBu), Phe (4-tBu), Phe Or Phe (4-Me); X12 is Arg, hLeu, (D) Asn, or any alpha methyl amino acid such as Aib, alpha-MeLys, alpha-MeLeu or alpha-MeOrn; X13 is Lys, Glu or Lys (Ac); X14 is Phe or Asn; X15 is? -Ala, Gln, Gly, Ser, Ala; And X16 are absent, or AEA. In certain embodiments, the peptide inhibitor of SEQ ID NO: III comprises one or more, two or more, three or more, four or more, five or more, six or more of the following features: X10 is Tyr or Phe analogs; X11 is Trp, 2-Nal, 1-Nal, Phe (4-O-allyl), Tyr (3-tBu), Phe (4-tBu), Phe Or Phe (4-Me); X12 is Arg, hLeu, (D) Asn, or any alpha methyl amino acid such as Aib, alpha-MeLys, alpha-MeLeu or alpha-MeOrn; X13 is Lys, Glu or Lys (Ac); X14 is Phe or Asn; X15 is GIy, Ser, Ala; X16 is absent, or AEA. In certain embodiments, Phe analogs Phe (4-OBzl), Phe (4-OMe), Phe (4-CONH 2), Phe (3,4-Cl 2), Phe (4-tBu), Phe (4 -NH2), Phe (4-Br), Phe (4-CN), Phe (4-carboxy), Phe [4- (2-aminoethoxy)] or Phe (4-guanadino). In certain embodiments, X11 is 2-Nal or 1-Nal. In certain embodiments, X1, X2, and X3 are absent. In certain embodiments, X4 is Abu and X9 is Cys.

In certain embodiments, the peptide inhibitor of SEQ ID NO: III comprises one or more, two or more, three or more, four or more, five or more, six or more of the following features: X10 is Tyr or Phe analogs; X11 is Trp, 2-Nal, 1-Nal, Phe (4-O-allyl), Tyr (3-tBu), Phe (4-tBu), Phe Or Phe (4-Me); Acl, Acbc, Acvc, Agp, Aib,? -Diethyl Gly,? -MeLys,? -MeLys (Ac) ,? -Me-Leu,? -MeOrn,? -MeSer,? -MeVal; X13 is Lys, Glu or Lys (Ac); X14 is Phe or Asn; X15 is GIy; X16 is absent, or AEA. In certain embodiments, Phe analogs Phe (4-OBzl), Phe (4-OMe), Phe (4-CONH 2), Phe (3,4-Cl2), Phe (4-tBu), Phe (4- NH ₂ ), Phe (4-Br), Phe (4-CN), Phe (4-carboxy), Phe (4- aminoamino) or Phe (4-guanadino). In certain embodiments, X11 is 2-Nal or 1-Nal. In certain embodiments, X1, X2, and X3 are absent. In certain embodiments, X4 is Abu and X9 is Cys.

In certain embodiments, the peptide inhibitor of SEQ ID NO: III has one or more, two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more , 10 or more, or 11: X5 is Arg or Gln; X6 is Thr; X7 is Trp; X8 is Gln; X10 is a Phe analog; X11 is selected from the group consisting of Trp, 2-Nal, 1-Nal, Phe (4-O-allyl), Tyr (3-tBu), Phe (4-Me); X12 is selected from the group consisting of Aib,? -MeLys,? -MeLeu, 4-amino-4-carboxy-tetrahydropyran, Acc Acpc Acbc Acvc Agp Aib,? -Diethyl Gly, ),? -Me-Leu,? -MeSer,? -MeVal,? -MeOrn; X13 is Lys, Glu or Lys (Ac); X14 is Phe or Asn; X15 is? -Alla, Gly, Ser, Ala; X16 is absent, or AEA. In certain embodiments, the peptide inhibitor of SEQ ID NO: III has one or more, two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more , 10 or more, or 11: X5 is Arg or Gln; X6 is Thr; X7 is Trp; X8 is Gln; X10 is a Phe analog; X11 is selected from the group consisting of Trp, 2-Nal, 1-Nal, Phe (4-O-allyl), Tyr (3-tBu), Phe (4-Me); X12 is Aib,? -MeLys,? -MeLeu or? -MeOrn; X13 is Lys, Glu or Lys (Ac); X14 is Phe or Asn; X15 is GIy, Ser, Ala; X16 is absent, or AEA. In certain embodiments, Phe analogs Phe (4-OBzl), Phe (4-OMe), Phe [4- ( 2-aminoethoxy)], Phe (4-CONH 2), Phe (3,4-Cl 2 ), and Phe (4-tBu), Phe (4-NH 2), Phe (4-Br), Phe (4-CN), Phe (4-CO 2 H), or Phe (4- iguana dino) . In certain embodiments, X11 is 2-Nal or 1-Nal. In certain embodiments, X1, X2, and X3 are absent. In certain embodiments, X4 is Abu and X9 is Cys.

In certain embodiments, the peptide inhibitor of SEQ ID NO: III has one or more, two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more , 10 or more, or 11: X5 is Arg or Gln; X6 is Thr; X7 is Trp; X8 is Gln; X10 is a Tyr or Phe analogue; X11 is selected from the group consisting of Trp, 2-Nal, 1-Nal, Phe (4-O-allyl), Tyr (3-tBu), Phe (4-Me); X12 is selected from the group consisting of Arg, hLeu, (D) Asn, 4-amino-4-carboxy-tetrahydropyran, Achc Acpc, Acbc, Acvc, Aib, -Me-Leu,? -MeSer,? -MeVal; X13 is Lys, Glu or Lys (Ac); X14 is Phe or Asn; X15 is? -Ala, Asn or Gly; X16 is absent, or AEA. In certain embodiments, the peptide inhibitor of SEQ ID NO: III has one or more, two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more , 10 or more, or 11: X5 is Arg or Gln; X6 is Thr; X7 is Trp; X8 is Gln; X10 is a Tyr or Phe analogue; X11 is selected from the group consisting of Trp, 2-Nal, 1-Nal, Phe (4-O-allyl), Tyr (3-tBu), Phe (4-Me); X12 is Arg, hLeu, (D) Asn,? -MeLys,? -MeLeu or? -MeOrn, Aib; X13 is Lys, Glu or Lys (Ac); X14 is Phe or Asn; X15 is GIy; X16 is absent, or AEA. In certain embodiments, Phe analogs Phe (4-OBzl), Phe (4OMe), Phe (4-CONH 2), Phe (3,4-Cl 2), Phe (4-tBu), Phe (4-NH _2), and Phe (4-Br), Phe (4-CN), Phe (4-CO 2 H), Phe (4- (2- amino-ethoxy)) or Phe (4- guanidino). In certain embodiments, X11 is 2-Nal or 1-Nal. In certain embodiments, X1, X2, and X3 are absent. In certain embodiments, X4 is Abu and X9 is Cys.

In certain embodiments, the invention encompasses a polynucleotide comprising 8 to 20 nucleotides, optionally comprising the core sequence of SEQ ID &lt; RTI ID = 0.0 &gt; IIIb &lt; / RTI &gt; , 8 to 16 or 8 to 12 amino acids,

Xaa4-Xaa5-Xaa6-Trp-Xaa8-Xaa9-Xaa10-Xaa11 (IIIb)

Wherein Xaa4 and Xaa9 are each independently selected from Abu and Cys, wherein Xaa4 and Xaa9 are not both identical; Xaa5, Xaa6 and Xaa8 are any amino acid residues; Xaa10 is Tyr, Phe analogue or 2-Nal, and Xaa11 is 2-Nal or Trp. In certain embodiments, Xaa10 is Phe (4-OMe), 2-Nal, or Phe [4- (2-aminoethoxy)]. In one embodiment, Xaa10 is Phe (4-OMe). In one embodiment, Xaa7 is Phe [4- (2-aminoethoxy)]. In one embodiment, Xaa11 is 2-Nal. In certain embodiments, the peptides are cyclized through Xaa4 and Xaa9. In certain embodiments, the Phe analog is Phe [4- (2-aminoethoxy)] or Phe (4-OMe). In certain embodiments, Xaa4 is Abu, Xaa9 is Cys, and the peptide is cyclized via Xaa4 and Xaa9. In certain embodiments, the peptide is a peptide inhibitor of SEQ ID NO: III, wherein, in certain embodiments, X1, X2, and X3 are absent. In certain embodiments, the peptides inhibit the binding of IL-23 to IL-23R. (D) Arg, Phe, (D) Phe, 2-Nal, Thr, Leu, or (D) Gln linked to Xaa4. . In certain embodiments, this is (D) Arg or (D) Phe.

In certain embodiments, the invention encompasses a polynucleotide comprising, or consisting of, the core sequence of SEQ ID &lt; RTI ID = 0.0 &gt; IIIc, &lt; / RTI & , 8 to 16 or 8 to 12 amino acids,

Abu-Xaa5-Xaa6-Trp-Xaa8-Cys- [Phe (4-OMe)] - (2-Nal)

Wherein Xaa5, Xaa6 and Xaa8 are any amino acid residues. In certain embodiments, the peptides are cyclized through Abu of Xaa4 and Cys of Xaa9. In certain embodiments, the peptide is a peptide inhibitor of SEQ ID NO: III, wherein, in certain embodiments, X1, X2, and X3 are absent. In certain embodiments, the peptides inhibit the binding of IL-23 to IL-23R. (D) Arg, Phe, (D) Phe, 2-Nal, Thr, Leu, or (D) Gln linked to Abu in a specific embodiment. . In certain embodiments, this is (D) Arg or (D) Phe.

In certain embodiments, the invention encompasses a polynucleotide comprising 8 to 20, preferably at least 10, at least 10, at least 10, at least 10, at least 10, , 8 to 16 or 8 to 12 amino acids,

Abu-Xaa5-Xaa6-Trp-Xaa8-Cys-Xaa10-Trp (IIId)

Wherein Xaa5, Xaa6 and Xaa8 are any amino acid residues; Xaa10 is a modified Phe. In certain embodiments, the variant is Phe Phe (4-tBu), Phe (4- guanidino), Phe [4- (2-aminoethoxy)], Phe (4-CO 2 H), Phe (4 is -CN), Phe (4-Br ), Phe (4-NH 2), PHe (CONH 2) or Phe (4-Me). In certain embodiments, the variant is Phe Phe (4-tBu), Phe (4- guanidino), Phe [4- (2-aminoethoxy)], Phe (4-CO 2 H), Phe (4 is -CN), Phe (4-Br ), Phe (4-NH 2), or Phe (4-Me). In one embodiment, Xaa10 is Phe [4- (2-aminoethoxy)] or Phe (4-OMe). In one embodiment, Xaa10 is Phe [4- (2-aminoethoxy)]. In certain embodiments, the peptides are cyclized through Abu of Xaa4 and Cys of Xaa9. In certain embodiments, the peptide is a peptide inhibitor of SEQ ID NO: III, wherein, in certain embodiments, X1, X2, and X3 are absent. In certain embodiments, the peptides inhibit the binding of IL-23 to IL-23R. (D) Arg, Phe, (D) Phe, 2-Nal, Thr, Leu, or (D) Gln linked to Abu in a specific embodiment. . In certain embodiments, this is (D) Arg or (D) Phe.

In certain embodiments, the invention is directed to an isolated, optionally 8 to 20, 8 to 16, or 8 to 12 amino acid, optionally comprising a core sequence of the following sequence IIIe, Lt; RTI ID = 0.0 &gt;

Abu-Xaa5-Xaa6-Trp-Xaa8-Cys-Phe [4- (2-aminoethoxy)] - [2-Nal]

Wherein Xaa5, Xaa6 and Xaa8 are any amino acid residues. In certain embodiments, the peptides are cyclized through Abu of Xaa4 and Cys of Xaa9. In certain embodiments, the peptide is a peptide inhibitor of SEQ ID NO: III, wherein, in certain embodiments, X1, X2, and X3 are absent. In certain embodiments, the peptides inhibit the binding of IL-23 to IL-23R. (D) Arg, Phe, (D) Phe, 2-Nal, Thr, Leu, or (D) Gln linked to Abu in a specific embodiment. . In certain embodiments, this is (D) Arg or (D) Phe.

In one embodiment, Xaa5 and Xaa8 are Gln. In one embodiment, Xaa6 is Thr. In certain embodiments, the peptides are cyclized through Abu of Xaa4 and Cys of Xaa9.

In certain embodiments of the peptide inhibitors of SEQ ID NO: III, the peptide inhibitor has the structure set forth in any of Tables 5a-5c, or comprises the amino acid sequences set forth in Tables 5a-5c.

In particular aspects, the invention provides a peptide inhibitor of the interleukin-23 receptor, or a pharmaceutically acceptable salt or solvate thereof, wherein the peptide inhibitor comprises an amino acid sequence of the sequence formula (Vf):

(Vf) X1-X2-X3-Abu-X5-X6-X7-X8-Cys-X10-X11-X12-X13-X14-

In this formula,

X1 is absent;

X2 is absent or X2 is D-Asp, E, R, D-Arg, F, D-Phe, 2-Nal, T, L, D-Gln or D-Asn;

X3 is D-Arg;

X5 is an N, Q, Cit, Lys or Lys conjugate such as Lys (IVA), Lys (biotin), Lys (octanyl), Lys (Palm), Lys (PEG), Lys -Palm), Lys (Ac));

X6 is T, S or V;

X7 is W, 1-Nal, or 2-Nal;

X8 is Q, Cit, N, Aib or Lys (Ac);

X10 is Phe [4- (2- amino-ethoxy)], Phe [4- (2- acetylamino-ethoxy) or Phe (4-CONH ₂₎ and;

X11 is 2-Nal;

X12 is a 4-amino-4-carboxy-tetrahydropyran, Aib, alphaMeLeu, alphaMeLys, or alphaMeLys conjugates such as alphaMeLys (Ac), alphaMeLys (PEG4-Palm), alphaMeLys (PEG4-lauryl), alphaMeLys GluPalm),? MeLys (PEG4 isoGlu lauryl),? MeLys (IVA),? MeLys (biotin), or? MeLys (octanyl);

X13 can be a Q, E, Cit or Lys conjugate such as Lys (Ac), Lys (PEG4-iso Glu-Palm), Lys (PEG4-octanyl), Lys Octanyl), Lys (Palm), Pys (PEG8), or Lys (PEG11-Palm));

X14 is N, Cit, Q, L, G, S, Aib, F, 2-Nap, N-Me-Ala, R, W, nLeu, Tic or Lys conjugates such as Lys (Ac);

X15 is N, Cit, Q,? Ala, Lys (Ac) or Aib;

X16, X17, X18, X19 and X20 are not present.

In certain embodiments, X2 is D-Asp, E, R, D-Arg, F, D-Phe, 2-Nal, T, L, D-Gln or D-Asn.

In particular aspects, the invention provides a peptide inhibitor of an interleukin-23 receptor, or a pharmaceutically acceptable salt or solvate thereof, wherein the peptide inhibitor comprises an amino acid sequence of the sequence formula (Vh):

X1-X2-X3-Abl-X5-X6-X7-X8-Cys-X10-X11-X12-X13-X14-X15-

X1 is any amino acid, or is absent;

X2 is any amino acid, or is absent;

X3 is any D-amino acid, or is absent;

X4 is a chemical moiety capable of forming a bond with Cys, hCys, Pen, hPen, Abu, Ser, hSer or X9;

X5 is Ala,? -MeOrn,? -MeSer, Cit, Dap, Dab, Dap (Ac), Gly, Lys, Asn, N-MeGln, N-MeArg, Orn, Gln, Arg, Ser, Glu or Thr;

X6 is Thr, Ser, Asp, Ile or any amino acid;

X7 is Trp, 6-chloro-Trp, 1-Nap or 2-Nap;

X8 is selected from the group consisting of Glu, Gln, Asn, Lys (Ac), Cit, Cav, Lys (N-epsilon- (N- alpha palmitoyl- L- gamma- glutamyl) ego;

X9 is a chemical moiety capable of forming a bond with Cys, hCys, Pen, hPen, Abu, or X4;

X10 is 2-Nal, Phe analog, Tyr, or Tyr analog;

X11 is 1-Nal, 2-Nal, Phe (3,4-dimethoxy), 5-hydroxy Trp, Phe (3,4-Cl2), Trp or Tyr (3-tBu);

X12 is selected from the group consisting of Aib, 4-amino-4-carboxy-tetrahydropyran, any alpha-methyl amino acid, alpha-ethyl-amino acid, Achc, Acvc, Acbc Acpc, Me, Me, Me, Ca, Ca, Cpa, D-Asn, Glu, His, hLeu, hArg, Lys, Leu, Octgly, Orn, piperidine, Arg, Ser, Thr or THP;

X13 is Lys (Ac), Gln, Cit, Glu, or any amino acid;

X14 is Asn, Gln, Lys (Ac), Cit, Cav, Lys (N-epsilon- (N- alpha -palmitoyl-L- gamma- glutamyl) Or any amino acid;

X15 is? -Ala, Asn, Gly, Gln, Ala, Ser, Aib, Asp or Cit;

X16 is any amino acid, or is absent;

X17 is any amino acid or is absent;

X18 is any amino acid or is absent;

X19 is any amino acid, or is absent;

X20 is any amino acid or is absent.

In certain embodiments of any of the peptide inhibitors described herein, including but not limited to, the sequence formula (If) and (Ih), the peptide inhibitor is cyclized via a bond between X4 and X9, e.g., a thioether bond . In certain embodiments, the peptide inhibitor inhibits the binding of interleukin-23 (IL-23) to the IL-23 receptor.

In certain embodiments, X1, X2, and X3 are absent. In certain embodiments, X1 and X2 are absent. In certain embodiments, Xl is a D-amino acid or is absent. In certain embodiments, X2 is a D-amino acid or is absent.

In certain embodiments, X5 is selected from the group consisting of Ala, alpha-MeOrn, alpha-MeSer, Cit, Dap, Dab, Dap (Ac), Gly, Lys, Asn, N-MeGln, N-MeArg, Orn, Gln, Or Thr;

In certain embodiments, X5 is N, X6 is T, X7 is W, or X8 is Q. In certain embodiments, X5 is N, X6 is T, X7 is W, and X8 is Q.

In certain embodiments, X5 is Q, X6 is T, X7 is W, or X8 is Q. In certain embodiments, X5 is Q, X6 is T, X7 is W, and X8 is Q.

In certain embodiments, X5 is N, X6 is T, X7 is W, and X8 is Cit.

In certain embodiments, X10 is Phe [4- (2-aminoethoxy)].

In certain embodiments, X 12 is 4-amino-4-carboxy-tetrahydropyran, Aib, αMeLeu, or αMeLys. In certain embodiments, X12 is 4-amino-4-carboxy-tetrahydropyran.

In certain embodiments, X13 is E or Lys (Ac). In certain embodiments, X13 is Lys (Ac).

In certain embodiments, X 14 is selected from the group consisting of Asn, Gln, Lys (Ac), Cit, Cav, Lys (N-epsilon- (N- alpha -palmitoyl- L- gamma- glutamyl) Tolyl), or any amino acid;

In certain embodiments, X15 is? -Ala, Asn, Gly, Gln, Ala, Ser, Aib, or Cit.

In certain embodiments, X 14 is N.

In certain embodiments, X 15 is N.

In certain embodiments, X16 is a D-amino acid or is absent. In certain embodiments, X17 is a D-amino acid, or is absent. In certain embodiments, X18 is a D-amino acid or is absent. In certain embodiments, X19 is a D-amino acid or is absent. In certain embodiments, X20 is a D-amino acid or is absent.

In certain embodiments, X2 is absent; X3 is absent; X5 is Q; X6 is T, X7 is W, X8 is Q; X10 is Phe [4- (2-aminoethoxy)]; X12 is 4-amino-4-carboxy-tetrahydropyran, Aib,? MeLeu, or? MeLys; X13 is E or Lys (Ac); X14 is N; X15 is N. In certain embodiments, X12 is 4-amino-4-carboxy-tetrahydropyran and X13 is Lys (Ac).

In certain embodiments, any amino acid of the peptide inhibitor is linked to a linker moiety, such as PEG.

In certain embodiments, the N-terminus of the peptide inhibitor comprises an Ac group.

In certain embodiments, the C-terminus of the peptide inhibitor comprises an NH ₂ group.

In certain embodiments, the invention provides peptides comprising or consisting of the amino acid sequences shown in any of Table 4s or Table 5s, or peptide inhibitors comprising (or consisting of) the structure shown in any of Table 4s or Table 5s Acceptable salts). In certain embodiments, the peptide does not comprise a conjugated moiety but comprises an Abu residue. In certain embodiments, the peptide or inhibitor comprises a thioether linkage between two Abu and Cys residues or between the two outermost amino acids in the parentheses following the term "cyclo " representing the presence of a cyclic structure. In certain embodiments, the inhibitor is an acetate salt. Exemplary inhibitor peptide sequences are shown in Tables 4 and 5 as N-terminal to C-terminal with conjugated moieties, and N-terminal Ac and / or C-terminal NH ₂ groups shown. The cyclic structure appears as "cyclo" as illustrated in Table 5, indicating the presence of a thioether bond between Abu in parentheses at X4 and Cys at X9.

[Table 4]

[Table 5a]

[Table 5b]

Exemplary peptide inhibitors containing cyclic amides

 In certain embodiments, the invention includes a peptide inhibitor of an interleukin-23 receptor, or a pharmaceutically acceptable salt or solvate thereof, wherein the peptide inhibitor has a structure of formula IV:

R ¹ -XR ² (IV)

Wherein R ¹ is a bond, hydrogen, C ¹ -C 6 alkyl, C 6 -C 12 aryl, C 6 -C 12 aryl C 1 -C 6 alkyl, C 1 -C 20 alkanoyl, and a PEGylated version of any of the foregoing, ;

R ² is a bond, OH or NH ₂ ;

X is an amino acid sequence consisting of 8 to 20 amino acids comprising or consisting of the sequence of SEQ ID NO:

(IVa) X1-X2-X3-X4-X5-X6-W-X8-X9-X10-X11-X12-

here,

X1 is absent or is any amino acid;

X2 is absent, or is any amino acid;

X3 is absent or is any amino acid;

X4 is Dap, Dab, Glu, Asp, (D) -Asp or (D) -Dab;

X5 is selected from Gln, Ala, Cys, Cit, Asp, Dab, Dap, Glu, Phe, Gly, His, hCys, Lys, Leu, Met, Asn, N-Me- N-Me-Gln, N-Me-Arg, Orn, Pro, Pen, Gln, Arg, Ser, Thr, or Val;

X6 is Thr, Asp, Glu, Phe, Asn, Pro, Arg, Ser, or Thr;

X7 is Trp, GIu, GIy, Ile, Asn, Pro, Arg, Thr or OctGly;

X8 is Gln, Glu, Phe, Lys, Asn, Pro, Arg, Thr, or Trp;

X9 is Dap, Dab, Glu, Asp, (D) -Asp or (D) -Dab;

X10 is selected from the group consisting of Tyr (OMe) Phe (4-OMe), 1-Nal, 2-Nal, Aic, a-MePhe, Bip, (D) Cys, Cha, DMT, hPhe (3,4- dimethoxy), hTyr, N-Me- Tyr, Trp, Phe (4-CONH 2), Phe (4- phenoxy), Thr, Tic, Tyr, Tyr (3-tBu), Phe (4-tBu), Phe ( 4-CN), Phe (4-Br), Phe (4-NH 2), Phe (4-F), Phe (3,5-F 2), Phe ( penta -F _{), Phe (3,4-Cl 2} ), Phe (4-CF 3), Bip, Cha, 4- pyridyl alanine, βhTyr, OctGly, Phe (4 -N 3), Phe (4-Br) or Phe [4- (2-aminoethoxy)];

X11 is 2-Nal, 1-Nal, 2,4- dimethyl-Phe, Bip, Phe (3,4- Cl 2), Phe (3,5-F 2), Phe (4-CONH 2), Phe (4 -F), 4- phenyl-cyclohexyl _{alanine, Phe (4-CF 3)} , α-MePhe, βhPhe, βhTyr, βhTrp, BIP, Nva (5- phenyl), Phe, His, hPhe, Tic, Tqa, Trp, Tyr, Phe (4-OMe), Phe (4-Me), Trp (2,5,7-tri-tert-butyl) ), Phe (4-guanidino), Tyr (Bzl), or OctGly;

(D) Asp, (D) Phe, (D) Thr, 3-Pal, Asp, Dab, Dap,? -Diethyl Gly, Glu, Phe, hLeu, hArg, hLeu, Ile,? -Ala,? -Glu,? Acv Acpc, Acbc, Acvc, &lt; / RTI &gt; &lt; RTI ID = 0.0 &gt; Diethyl Gly,? -MeLys,? -MeLys (Ac),? -Me-Leu,? -MeSer,? -MeVal;

X13 is selected from the group consisting of Lys (Ac), (D) Asn, (D) Leu, (D) Thr, (D) Phe, Ala, Aib,? -MeLeu, Aib,? -Ala,? -Glu,? HAla,? HLeu, Lys (Ac), Leu, Asn, Ogl, Pro, Gln, Arg, Ser, Glu, Phe, hLeu, spiro-pip, Thr, Tba, Tlc, Val or Tyr;

X14 is Asn, Glu, Phe, Gly, His, Lys, Leu, Met, Asn, Pro, Gln, Arg, Ser, Thr, Tic or Tyr;

(D) Asp, (D) Leu, (D) Phe, (D) Thr, Ala, AEA, Asp, Glu, Phe, Gly, Lys, Leu, Pro, Gln, Arg or Ser;

X16 is absent or is Gly, Ala, Asp, Ser, Pro, Asn or Thr;

X17 is absent or is Glu, Ser, Gly or Gln;

X18 is absent, or is any amino acid;

X19 is absent or is any amino acid;

X20 is absent or is any amino acid.

(D) Asn, (D) Leu, (D) Asp, (D) Phe, (D) Ala, ) Thr, 3-Pal, Aib,? -Ala,? -Glu,? HAla,? HLeu,? HVal,? -Spiro-piper, Cha, Chg, Asp, Dab, Dap,? -Diethyl Gly, Glu, Phe, hLeu , hArg, hLeu, Ile, Lys, Leu, Asn, N-MeLeu, N-MeArg, Ogl, Orn, Pro, Gln, Arg, Ser, Thr or Tle; X13 is selected from the group consisting of Lys (Ac), (D) Asn, (D) Leu, (D) Thr, (D) Phe, Ala, Aib,? -MeLeu, Aib,? -Ala,? -Glu,? HAla,? HLeu, , Spiro-pip, Cha, Chg, Asp, Dab, Dap,? -diethyl Gly, Glu, Phe, hLeuLys, Leu, Asn, Ogl, Pro, Gln, Arg, Ser, , Tba, Tlc, Val or Tyr; X14 is Asn, Glu, Phe, Gly, His, Lys, Leu, Met, Asn, Pro, Gln, Arg, Ser, Thr, Tic or Tyr; X15 is Gly, (D) Ala, (D) Asn, (D) Asp, (D) Leu, (D) Phe, (D) Thr, Ala, AEA, Asp, Glu, Phe, Gly, Pro, Gln, Arg or Ser.

In certain embodiments of the peptide inhibitors of the sequence formula (IV): X5 is Cys, Cit, Asp, Dab, Dap, Gly, His, hCys, Lys, Met, Asn, N-Me- N-Me-Lys, N-Me-Gln, N-Me-Arg, Orn, Pro, Pen, Gln, Val; X6 is Glu, Arg, Ser; X7 is Trp, GIu, GIy, Ile, Asn, Pro, Arg, Thr or OctGly; X8 is Phe, Asn, Pro, Arg, Thr, Trp; X10 is selected from the group consisting of Phe (4-OMe), 1-Nal, 2-Nal, Aic, a-MePhe, Bip, (D) Cys, Cha, DMT, (D) Tyr, Glu, His, ethoxy), hTyr, N-Me- Tyr, Trp, Phe (4-CONH 2), Phe- (4- phenoxy), Thr, Tic, Tyr ( 3-tBu), Phe (4-tBu), Phe ( 4-CN), Phe (4 -Br), Phe (4-NH 2), Phe (4-F), Phe (3,5-F 2), PheCH 2 CO 2 H, Phe ( penta -F), _{Phe (3,4-Cl 2),} Phe (4-CF 3), Bip, Cha, 4- pyridyl alanine, βhTyr, OctgGly, Tyr (4 -N 3), Phe (4-Br), Phe [4 - (2-aminoethoxy)]; X11 is 2-Nal, 1-Nal, 2,4- dimethyl-Phe, Bip, Phe (3,4- Cl 2), Phe (3,5-F 2), Phe (4-CONH 2), Phe (4 -F), 4- _{phenyl-cyclohexyl, Phe (4-CF 3)} , α-MePhe, Nal, βhPhe, βhTyr, βhTrp, BIP, Nva (5- phenyl), Phe, His, hPhe, Tic, Tqa, Tyr Phe (4-OMe), Phe (4-Me), Tyr (2,5,7-tri-tert-butyl) ), Phe (4-guanidino), Tyr (Bzl), OctGly; X12 is selected from the group consisting of? -Me-Lys, D-Ala, (D) Asn, (D) Asp, (D) Leu, (D) Phe, -Ala,? HAla,? HArg,? HLeu,? HVal,? -Spiro-pip, Glu, hArg, Ile, Lys, N-MeLeu, N-MeArg, Ogl, Orn, Pro, Gln, Ser, Thr, Ac-Acpc, Acbc, Acvc, a-diethyl Gly,? -MeLys (Ac),? -MeSer,? -MeVal; X13 is selected from the group consisting of Lys, Lys (Ac), (D) Asn, (D) Leu, (D) Phe, (D) Thr, Ala,? -MeLeu, Aib,? -Ala,? -Glu,? HLeu, -Spiro-pip, Cha, Chg, Asp, Dab, Dap,? -Diethyl Gly, hLeu, Asn, Ogl, Pro, Gln, Ser, Thr, Tba, Tle; X14 is Glu, Gly, His, Lys, Leu, Met, Asn, Pro, Gln, Arg, Ser, Thr, Tic; Asp, (D) Leu, (D) Phe, (D) Thr, Aea, Asp, Glu, Phe, Gly, Lys, Leu, Pro, Asn, Arg or [beta] -Ala; X16 is GIy, Ser, Pro, Asn, Thr; X17 is Glu, Ser, Gly, Gln.

In certain embodiments of the peptide inhibitors of the sequence formula (IV): X5 is Cys, Cit, Asp, Dab, Dap, Gly, His, hCys, Lys, Met, Asn, N-Me- N-Me-Lys, N-Me-Gln, N-Me-Arg, Orn, Pro, Pen, Gln, Val; X6 is Glu, Arg, Ser; X7 is Trp, GIu, GIy, Ile, Asn, Pro, Arg, Thr or OctGly; X8 is Phe, Asn, Pro, Arg, Thr, Trp; X10 is selected from the group consisting of Phe (4-OMe), 1-Nal, 2-Nal, Aic, a-MePhe, Bip, (D) Cys, Cha, DMT, (D) Tyr, Glu, His, ethoxy), hTyr, N-Me- Tyr, Trp, Phe (4-CONH 2), Phe- (4- phenoxy), Thr, Tic, Tyr ( 3-tBu), Phe (4-tBu), Phe ( 4-CN), Phe (4 -Br), Phe (4-NH 2), Phe (4-F), Phe (3,5-F 2), PheCH 2 CO 2 H, Phe ( penta -F), _{Phe (3,4-Cl 2),} Phe (4-CF 3), Bip, Cha, 4- pyridyl alanine, βhTyr, OctgGly, Tyr (4 -N 3), Phe (4-Br), Phe [4 - (2-aminoethoxy)]; X11 is 2-Nal, 1-Nal, 2,4- dimethyl-Phe, Bip, Phe (3,4- Cl 2), Phe (3,5-F 2), Phe (4-CONH 2), Phe (4 -F), 4- _{phenyl-cyclohexyl, Phe (4-CF 3)} , α-MePhe, Nal, βhPhe, βhTyr, βhTrp, BIP, Nva (5- phenyl), Phe, His, hPhe, Tic, Tqa, Tyr Phe (4-OMe), Phe (4-Me), Tyr (2,5,7-tri-tert-butyl) ), Phe (4-guanidino), Tyr (Bzl), OctGly; X12 is selected from the group consisting of? -Me-Lys, D-Ala, (D) Asn, (D) Asp, (D) Leu, (D) Phe, -Ala,? HAla,? HArg,? HLeu,? HVal,? -Spiro-pip, Glu, hArg, Ile, Lys, N-MeLeu, N-MeArg, Ogl, Orn, Pro, Gln, Ser, Thr and Tle; X13 is selected from the group consisting of Lys (Ac), (D) Asn, (D) Leu, (D) Phe, (D) Thr, Ala,? -MeLeu, Aib,? -Ala,? -Glu,? HLeu, -Pip, Cha, Chg, Asp, Dab, Dap,? -diethyl Gly, hLeu, Asn, Ogl, Pro, Gln, Ser, Thr, Tba, Tle; X14 is Glu, Gly, His, Lys, Leu, Met, Asn, Pro, Gln, Arg, Ser, Thr, Tic; (D) Ala, (D) Asn, (D) Asp, (D) Leu, (D) Phe, (D) Thr, Aea, Asp, Glu, Phe, Gly, Lys, Leu, Pro, Arg; X16 is GIy, Ser, Pro, Asn, Thr; Or X17 is Glu, Ser, Gly, Gln.

In certain embodiments, the peptide inhibitor is cyclized. In certain embodiments, the peptide is cyclized via an intramolecular bond between X4 and X9. In certain embodiments, the intramolecular bond is an amide bond.

In certain embodiments, the peptide inhibitor is linear or non-pecylated.

In certain embodiments of the peptide inhibitor of SEQ ID NO: IV, no more than one, two or more, or all three of X1, X2, and X3 are present.

In certain embodiments, X3 is Glu, (D) Glu, Arg, (D) Arg, Phe, (D) Phe, 2-Nal, Thr, Leu or (D) Gln. In certain embodiments, X3 is (D) Arg or (D) Phe.

In certain embodiments of the peptide inhibitor of SEQ ID NO: IV, no more than one, two or more, or all three of X17, X19 and X20 are present.

In certain embodiments of the peptide inhibitor of SEQ ID NO: IV, X4 is Dap, Dab, or (D) Dab, and X9 is Glu, (D) Asp, or Asp. In certain embodiments of the peptide inhibitors of SEQ ID NO: I, X4 is Glu, (D) Asp or Asp and X9 is Dab, Dap or (D) Dab.

In certain embodiments of the peptide inhibitor of SEQ ID NO: IV, X18 is (D) -Lys. In certain embodiments, X17 is absent and X18 is (D) -Lys.

In certain embodiments of the peptide inhibitors of SEQ ID NO: IV, the peptide inhibitor comprises at least one, at least two, at least three, or all four of the following features: X5 is Gln; X6 is Thr; X7 is Trp; X8 is Gln.

In certain embodiments of the peptide inhibitors of SEQ ID NO: IV, the peptide inhibitor comprises one or more, two or more, three or more, four or more, five or more, six or more of the following features: Tyr, Phe [4- (2-aminoethoxy)], Phe (4-CONH 2) , or Phe (4-OMe), and; X11 is 2-Nal or Trp; X12 is selected from the group consisting of 4-amino-4-carboxy-tetrahydropyran, Achc Acpc, Acbc, Acvc, Aib,? -Diethyl Gly,? -MeLys,? -MeLys alpha-MeSer, alpha-MeVal, or Arg; X13 is Glu or Lys (Ac); X14 is Asn; X15 is Gly, Asn, or [beta] -Ala; X16 is AEA. In certain embodiments of the peptide inhibitors of SEQ ID NO: IV, the peptide inhibitor comprises one or more, two or more, three or more, four or more, five or more, six or more of the following features: Tyr; X11 is Trp; X12 is Arg; X13 is GIu; X14 is Asn; X15 is GIy; X16 is AEA.

In certain embodiments of the peptide inhibitors of SEQ ID NO: 4, the peptide inhibitor comprises at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, 9 or more, 10 or more, or all thereof: X5 is Gln; X6 is Thr; X7 is Trp; X8 is Gln; X10 is Tyr; X11 is Trp; X12 is Arg; X13 is Glu or Lys (Ac); X14 is Asn; X15 is GIy; X16 is AEA. In certain embodiments of the peptide inhibitors of SEQ ID NO: 4, the peptide inhibitor comprises at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, 9 or more, 10 or more, or all thereof: X5 is Gln; X6 is Thr; X7 is Trp; X8 is Gln; X10 is Tyr; X11 is Trp; X12 is Arg; X13 is GIu; X14 is Asn; X15 is GIy; X16 is AEA.

In certain embodiments of the peptide inhibitors of SEQ ID NO: 4, the peptide is cyclized through X4 and X9; X5, X6, X7 and X8 are Gln, Thr, Trp, and Gln, respectively; X10, X11, X12, X13, X14, X15 and X16 are Tyr, Trp, Arg, Glu, Asn, Gly and AEA, respectively.

In certain embodiments, the invention encompasses an antibody that comprises, or alternatively consists of, or is having the core sequence of SEQ ID NO: 4b, which inhibits the binding of IL-23 to IL-23R , &Lt; / RTI &gt; consisting of 8 to 20 amino acids,

Xaa4-Xaa5-Xaa6-Trp-Xaa8-Xaa9- [Phe (4-OMe)] - [2-Nal]

Wherein Xaa4 and Xaa9 are each independently selected from Dap, Dab, Glu, Asp, (D) -Asp and (D) -Dab wherein Xaa4 and Xaa9 form an intramolecular bond such as a cyclic amide You can; Xaa5, Xaa6 and Xaa8 are any amino acid residues. In certain embodiments, the peptide inhibitor is a peptide inhibitor of the sequence formula IV. In certain embodiments, the peptides inhibit the binding of IL-23 to IL-23R.

In certain embodiments of the peptide inhibitors of SEQ ID NO: 4, the peptide inhibitor has the structure set forth in Table 7, or comprises the amino acid sequence set forth in Table 7.

Certain exemplary peptide inhibitors of the present invention also include peptides of the present invention having a sequence of formula Va, Vb, Vc, Vd, Ve, Vf, Vg ) And (Vh), and in Tables 2-5. Such peptide inhibitors are acetate salts.

Optional features of peptide inhibitors

Any of the peptide inhibitors of the present invention may be further defined, for example, as described below. Each of the further defined features described herein can be applied to any peptide inhibitor, where it is understood that the amino acid assigned at a particular position allows for the presence of additional defined features.

In certain embodiments of any of the peptide inhibitors described herein, the peptide inhibitor is cyclized.

In certain embodiments of any of the peptide inhibitors described herein, the peptide inhibitor or monomeric subunit thereof is linear or non-pecylated. Linear or non-pelletized, X4 and X9 may be any amino acid.

In certain embodiments, the peptide inhibitor is, for example, cyclized via X4 and X9.

In various embodiments, R ¹ is selected from the group consisting of a bond, hydrogen, C ¹ -C 6 alkyl, C 6 -C 12 aryl, C 6 -C 12 aryl C 1 -C 6 alkyl, or C 1 -C 20 alkanoyl and the PEGylated version of any of the above, Include those as spacers, such as acetyl. R &lt; ¹ &gt; may be substituted, or may be present other than the typical amine group located at the amino terminus of the peptide. Further understand that R &lt; ¹ &gt; may not be present. In certain embodiments, the peptide inhibitor is selected from the group consisting of hydrogen, C 1 -C 6 alkyl, C 6 -C 12 aryl, C 6 -C 12 aryl C 1 -C 6 alkyl, or C 1 -C 20 alkanoyl, and a PEGylated version of any of the foregoing, Including, for example, acetyl. In certain embodiments of any of the peptide inhibitors described herein, the R ¹ or N-terminal moiety is hydrogen. In certain embodiments, R &lt; ¹ &gt; is a bond, e.g., a covalent bond.

In certain embodiments of any of the peptide inhibitors having any of the various sequences set forth herein, the R ¹ or N-terminal moiety is selected from the group consisting of methyl, acetyl, formyl, benzoyl, trifluoroacetyl, isovaleryl, Isobutyryl, octanyl, and conjugated amides of lauric acid, hexadecanoic acid, and gamma-Glu-nuclear dedecanoic acid. In one embodiment, the R ¹ or N-terminal moiety is pGlu. In certain embodiments, R &lt; ¹ &gt; is hydrogen. In certain embodiments, R ¹ is acetyl, whereby the peptide inhibitor is acylated at its N-terminus, thereby capping or protecting, for example, an N-terminal amino acid residue, such as an N-terminal Pen or Abu residue.

In certain embodiments of any of the peptide inhibitors described herein, the R ¹ or N-terminal moiety is an acid. In certain embodiments, the R ¹ or N-terminal moiety is selected from the group consisting of acetic, formic, benzoic, trifluoroacetic, isovaleric, isobutyric, octanoic, lauric, And salts thereof with organic acids such as 4-fluorophenylacetic acid, gallic acid, pyroglutamic acid, cyclopentane propionic acid, glycolic acid, oxalic acid, pyruvic acid, lactic acid, malonic acid, succinic acid, malic acid, maleic acid, fumaric acid, Ene-1-carboxylic acid, glucoheptonic acid, 3-phenylpropionic acid, trimethylacetic acid, 3-hydroxybenzoyl) benzoic acid, cinnamic acid, mandelic acid, 4-methylbicyclo Acetic acid, tartaric acid, succinic acid, tartaric acid, charybutyl acetic acid, lauryl sulfuric acid, gluconic acid, glutamic acid, hydroxynaphthoic acid, salicylic acid, stearic acid, muconic acid, alkylsulfonic acid and arylsulfonic acid.

In certain embodiments, the R ¹ or N-terminal moiety is an alkylsulfonic acid selected from methanesulfonic acid, ethanesulfonic acid, 1,2-ethane-disulfonic acid, and 2-hydroxyethanesulfonic acid.

In certain embodiments, the R ¹ or N-terminal moiety is an arylsulfonic acid selected from benzenesulfonic acid, 4-chlorobenzenesulfonic acid, 2-naphthalenesulfonic acid, 4-toluenesulfonic acid, and camphorsulfonic acid.

In some embodiments wherein the peptide of the invention is conjugated to an acidic compound, such as isovaleric acid, isobutyric acid, valeric acid, etc., the presence of said conjugate is referred to as the acidic form. Thus, for example, but not by way of limitation, iso valeroyl- [Pen] -QTWQ [Pen] - [Phe (4- OMe)] - [2- Instead of specifying conjugation of isovaleric acid to a peptide by mentioning isovaleroyl, such as MeLys] - [Lys (Ac)] - NG-NH ₂ , in some embodiments, Refers to the conjugation as Pen-QTWQ [Pen] - [Phe (4-OMe)] - [2-Nal] - [α-MeLys] - [Lys (Ac)] -GG-NH ₂ . Reference to the conjugation of its acidic form is intended to include forms present in the peptide inhibitor.

In certain embodiments, the peptide inhibitor comprises a bond, a C-terminal (e.g., R ² or C-terminal moiety) selected from OH or NH ₂ . In certain embodiments, R &lt; ² &gt; is a bond. In various embodiments of any of the peptide inhibitors having any of the various sequences set forth herein, the R ² or C-terminal moiety is OH or NH _{2 .} It is understood that the R ² or C-terminal moieties may be substituted, or may be present other than the typical carboxyl groups typically located at the carboxy terminus of the peptide. Further understand that R &lt; ² &gt; may not be present.

In certain embodiments of any of the peptide inhibitors having any of the various sequences set forth herein, X is selected from the group consisting of 7 to 35 amino acid residues, 8 to 35 amino acid residues, 9 to 35 amino acid residues, 10 From 8 to 25 amino acid residues, from 9 to 25 amino acid residues, from 10 to 25 amino acid residues, from 7 to 20 amino acid residues, from 8 to 25 amino acid residues, from 10 to 25 amino acid residues, from 7 to 20 amino acid residues, from 8 to 25 amino acid residues, Comprising from 20 to about 20 amino acid residues, from about 9 to about 20 amino acid residues, from about 7 to about 18 amino acid residues, from about 8 to about 18 amino acid residues, from about 9 to about 18 amino acid residues, or from about 10 to about 18 amino acid residues, That is done.

In certain embodiments of any of the sequences described herein, either or both of X does not include or does not comprise the amino acid sequence set forth in U.S. Patent Application Publication No. US2013 / 0029907. In certain embodiments of any of the sequences set forth herein, either or both of X do not include, or do not comprise, the amino acid sequence set forth in U.S. Patent Application Publication No. US2013 / 0172272.

In certain embodiments of any of the peptide inhibitors described herein, the peptide inhibitor, or each monomer subunit thereof, comprises at least three, at least four, at least five, at least six, or at least six, at the carboxy terminus of the X9 amino acid residue Or consists of, seven amino acid residues. In certain embodiments of any of the peptide inhibitors described herein, the peptide inhibitor can comprise from 3 to 11, from 3 to 10, from 3 to 9, from 3 to 8, from 3 to 7, 3 to 6, 3 to 5, 3 to 4, 3, 4, 5, 6, 7, 8, 9, 10, or 11 amino acid residues.

In certain embodiments of any of the peptide inhibitors described herein, the peptide inhibitor, or each monomer subunit thereof, comprises or consists of four amino acid residues between X4 and X9. In one embodiment, X4 and X9 are both cysteine.

In certain embodiments, the peptide inhibitor of any of the sequences described herein comprises an amino acid residue or moiety designated X4 to X15. In certain embodiments, the peptide inhibitor does not comprise Xl to X3 or X16 to X20. In certain embodiments, the peptide inhibitor comprises an N-terminal extension of one to three amino acid residues corresponding to any of Xl to X3. In certain embodiments, any one or more of X1, X2, and X3, if present, are D-amino acids. In certain embodiments, the peptide inhibitor comprises a C-terminal extension of one to five amino acid residues corresponding to any of X16 to X20. In certain embodiments, any one or more of X16, X17, X18, X19, and X20, if present, is a D-amino acid. Exemplary amino acid residues that may be present at the N-terminal and / or C-terminal extensions are shown in Table 3 and Table 5. These tables each represent a first peptide inhibitor having derivatives thereof with N-terminal extension, C-terminal extension and / or conjugated moieties. The present invention includes derivatives of any of the peptide inhibitors described herein, including one or more N-terminal extensions, C-terminal extensions and / or conjugated moieties. In certain embodiments, any amino acid residue shown at an extended position in Table 3 and Table 5 may be present in any combination of peptide inhibitors of the present invention. In certain embodiments, the N-terminal and / or C-terminal extension is associated with, for example, an increased half-life on administration to the subject.

In certain embodiments of any of the peptide inhibitors described herein, the peptide inhibitor, or each monomer subunit thereof, comprises an amino acid sequence motif, W-X-X-Y-W, such as position X7-X11. In certain embodiments, the peptide inhibitor, or each monomeric subunit thereof, comprises an amino acid sequence motif, C-X-X-W-X-C-Y-W, e.g., position X4-X11. In certain embodiments, the peptide inhibitor, or each monomer subunit thereof, comprises an amino acid sequence motif, Pen-X-X-W-X-Pen-Y-W, e.g., position X4-X11. In certain embodiments of any of the peptide inhibitors described herein, the peptide inhibitor, or monomeric subunit thereof, does not comprise an amino acid sequence motif, WXXYW, e.g., position X7-X11, wherein X is any Amino acids.

In certain embodiments of any of the sequence or peptide inhibitors described herein, the peptide inhibitor comprises at least one amino acid residue at the N-terminus relative to X4. In certain embodiments, X3 is present. In certain embodiments, X3 is Glu, (D) Glu, Arg, (D) Arg, Phe, (D) Phe, 2-Nal, Thr, Leu or (D) Gln. In certain embodiments, X3 is (D) Arg or (D) Phe.

In certain embodiments of any of the sequence or peptide inhibitors described herein, the peptide inhibitor comprises an amino acid at X2. In certain embodiments, X2 is Glu, (D) Asp, Arg, (D) Arg, Phe, (D) Phe, 2-Nal, Thr, Leu, (D) Gln or (D) Asn. In certain embodiments, X2 and X3 are present. (D) Glu, (D) Asp, Arg, (D) Arg, Phe, (D) Phe, 2-Nal, Thr, Leu, (D) Arg.

In certain embodiments, one or both of the peptide inhibitors of the invention, or monomeric subunits thereof, are optionally substituted at its C-terminus with one or more of the following amino acid sequences:

ENG;

ENN;

[4-amino-4-carboxy-tetrahydropyran] -ENN;

[Lys (Ac)] - NN;

[[alpha] -MeLys] -ENG;

[? -MeLys] - [Lys (Ac)] - NN;

[? -MeLeu] - [Lys (Ac)] - NN

[[alpha] -MeLeu] -ENG;

[? -MeOrn] - [Lys (Ac)] - NG;

[[alpha] -MeLeu] -ENG;

Aib- [Lys (Ac)] - NG;

Aib- [Lys (Ac)] - NN;

NG- [AEA] - [(D) -Lys];

[Dapa] -NG- [AEA] - [(D) -Lys];

[Orn] -NG- [AEA] - [(D) -Lys];

[[alpha] -MeLys] -ENN;

[4-Amino-4-carboxy-tetrahydropyran] - [Lys (Ac)] - NN;

[Achc] - [Lys (Ac)] - NN; or

[Acpc] - [Lys (Ac)] - NN.

In certain embodiments, one of the amino acid sequences constitutes the terminal C-terminal amino acid of the peptide. In certain embodiments, the amino acid sequence corresponds to X13-X15 or X12-X15 or X14-X16 or X13-X17.

In certain embodiments, one or both of the peptide inhibitors of the invention, or monomeric subunits thereof, are optionally substituted at its C-terminus with one or more of the following amino acid sequences:

WQCY- [2-Nal] - [[alpha] -MeLys];

WQC- [Phe (4-OMe)] - [2-Nal] - [[alpha] -MeLys];

WQC- [Phe (4-OMe)] - [2-Nal] - [Aib];

WQ- [Pen] - [Phe (4-OMe)] - [2-Nal] - [[alpha] -MeLys];

W-Xaa8-C-Phe [4- (2-aminoethoxy)] - [2-Nal];

W-Xaa8-C-Phe [4- (2-aminoethoxy)] - [1-Nal];

W-Xaa8-C-Phe [4- (2-aminoethoxy)]; or

It comprises one of the W-Xaa8-C- [Phe ( 4-OCH 3)]. In certain embodiments, one of the amino acid sequences constitutes the terminal C-terminal amino acid of the peptide. In certain embodiments, the amino acid sequence corresponds to X7 to X12 or X7 to X11 or X7 to X10.

In certain embodiments of any of the peptide inhibitors described herein, including both a peptide monomer inhibitor, and a monomeric subunit of a peptide dimer inhibitor, the peptide monomer inhibitor or monomer subunit comprises an N-terminal amino acid residue Lt; RTI ID = 0.0 &gt; C-terminal &lt; / RTI &gt; amino acid residue. In certain embodiments, the peptide inhibitor (or a monomeric subunit thereof) comprises an intramolecular bond between X4 and X9, and a peptide bond between its N-terminal amino acid residue and its C-terminal amino acid residue. In certain embodiments, the intramolecular linkages are any of those described herein, such as disulfide or thioether linkages.

In certain embodiments, the invention comprises a peptide inhibitor comprising a core consensus sequence selected from one of the following (presented in C-terminal direction at the N-terminus):

X1-X2-X3-Pen-X5-X6-W-X8-Pen-X10-X11-X12-X13-X14-X15;

Pen-X5-X6-W-Q-Pen;

Pen-X5-X6-W-X8-Pen;

Pen-X5-X6-W-X8-Pen- [Phe (4-CONH2)]; And

Pen-X5-X6-W-X8-Pen- [Phe [4- (2-aminoethoxy)]]

In this formula, the Pen residue is bound by an intramolecular bond, e.g., a disulfide bond. X1, X2, X3, X5, X6, X8, X10, X11, X12, X13, X14, and X15 may be any amino acid. In some embodiments, X5 is Arg, Asn, Gln, Dap, Orn; X6 is Thr or Ser; X8 is Gln, Val, Phe, Glu, Lys. In certain embodiments, X1, X2, X3, X5, X6, X8, X10, X11, X12, X13, X14, and X15 are defined as described in any of the various sequence and peptide inhibitors described herein .

In certain embodiments, the invention comprises a peptide inhibitor comprising a core consensus sequence selected from one of the following (presented in C-terminal direction at the N-terminus):

X1-X2-X3-Abu-X5-X6-W-X8-C-X9-X10-X11-X12-X13-X14-X15;

Abu-X5-X6-W-Q-C;

Abu-X5-X6-W-X8-C;

Abu-X5-X6-W-X8-C- [Phe (4-CONH2)]; And

Abu-X5-X6-W-X8-C- [Phe [4- (2-aminoethoxy)]]

Here, Abu and C are linked through a thioether bond in the molecule. X1, X2, X3, X5, X6, X8, X10, X11, X12, X13, X14, and X15 may be any amino acid. In some embodiments, X5 is Arg, Asn, Gln, Dap, Orn; X6 is Thr or Ser; X8 is Gln, Val, Phe, Glu, Lys. In certain embodiments, X1, X2, X3, X5, X6, X8, X10, X11, X12, X13, X14, and X15 are defined as described in any of the various sequence and peptide inhibitors described herein .

In certain embodiments, any of the peptide inhibitors described herein may be further cyclized via peptide bonds between its N-terminal amino acid residue and its C-terminal amino acid residue. In certain embodiments, the peptide inhibitor comprises a peptide bond between X3 or X4 and any one of X9, X10, X11, X12, X13, X14, X15, X16, X17, X18, X19 or X20. In certain embodiments, a peptide inhibitor of the invention comprises a peptide bond between its N-terminal and C-terminal amino acid residues, which also includes an intramolecular bond between X4 and X9. In certain embodiments, the intramolecular bond is any of a disulfide bond, a thioether bond, a lactam bond or any other bond described herein.

Peptide dimer

In certain embodiments, the invention includes dimers consisting of the monomeric peptide inhibitors described herein, including dimers of any of the monomeric peptide inhibitors described in the tables, figures, or sequence listings described herein or appended hereto. As used herein. The dimer is included within the scope of the generic term "peptide inhibitor ". Exemplary dimers of the present invention are also shown in the accompanying table, wherein the dimerized monomer subunits in parentheses are followed by a linker. Unless otherwise specified, the subunit is linked through its C-terminus. As in peptide dimers, the term "dimer" refers to a compound to which two peptide monomer subunits are linked. The peptide dimer inhibitor of the present invention comprises two identical monomer subunits, so that a homodimer can be obtained, or two different monomer subunits can be included to obtain a heterodimer. The cysteine dimer comprises two peptide monomer subunits linked through a disulfide bond between the cysteine residue in one monomer subunit and the cysteine residue in the other monomer subunit.

In some embodiments, the peptide inhibitors of the present invention may be active when in dimeric stereoisomeric form, particularly when the free cysteine residue is present in the peptide. In certain embodiments, the inhibitor may be present as a synthesized dimer, or the free cysteine monomer peptides are present and are dimerized under oxidizing conditions. In some embodiments, the dimer is a homodimer. In another embodiment, the dimer is a heterodimer.

In certain embodiments, the peptidic dimer inhibitors of the present invention may be administered in combination with one or more of the peptide dimer inhibitors disclosed herein, such as those described in Tables 3a-3h, 4a, 4b, 5a-5c, 6,7, 8,9, 10,11, Including but not limited to two peptidic inhibitors of the present invention, including, but not limited to, a homodimer or heterodimer comprising any of the peptide sequences set forth in SEQ ID NOS:

The specific amino acid sequences listed in Tables 3a-3h, 4a, 4b, 5a-5c, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 are presented in one- However, if only a monomeric peptide inhibitor sequence is presented, in certain embodiments, the monomeric peptide inhibitor, i.e., monomeric subunit, is generally selected from, for example, Tables 3a-3h, 4a, 4b, 5a-5c, 8, 9, 10, 11, 12, 13, 14 or 15, and according to the present teachings, are dimerized to form a peptide dimer inhibitor.

In certain embodiments, the monomeric subunits of the present invention are modified by suitable linking moieties such as a disulfide bridge between two cysteine residues, each one in each peptide monomer subunit, , But may be dimerized by another suitable linker moiety. Some of the monomer subunits are shown to have C- and N-termini, both of which contain free amines. Thus, for the production of a peptide dimer inhibitor, the monomer subunits can be modified to remove C- or N-terminal free amines so that dimerization can occur in the free amines remaining. Additionally, in some cases, the terminal ends of the one or more monomeric subunits are selected from the group consisting of trifluoropentyl, acetyl, octonyl, butyl, pentyl, hexyl, palmityl, trifluoromethylbutyric acid, cyclopentanecarboxylic acid, Acylated organic compounds selected from acylated organic compounds selected from the group consisting of 4-fluorobenzoic acid, 4-fluorophenylacetic acid, 3-phenylpropionic acid, tetrahedrone-2H-pyran-4-carboxylic acid, succinic acid, It is true. In some cases, the monomeric subunit includes both a free carboxy terminal and a free amino terminal, whereby the user can selectively modify the subunit to achieve dimerization at the desired terminal. Thus, those skilled in the art will appreciate that the monomer subunits of the present invention can be selectively modified to achieve a single specific amine for the desired dimerization.

It is further understood that the C-terminal residue of the monomeric subunits disclosed herein is optionally an amide. In addition, in certain embodiments, it is understood that dimerization at the C-terminus is facilitated by the use of suitable amino acids including side chains with amine functionalities, as generally understood in the art. With respect to the N-terminal residue, in general, dimerization can be achieved either through free amine of the terminal residue, as generally understood in the art, or by using a suitable amino acid side chain with free amine I understand that.

The linker moiety linking the monomer subunits may comprise any structure, length, and / or size that is compatible with the teachings herein. In at least one embodiment, the linker moiety is selected from the group consisting of cysteine, lysine, DIG, PEG4, PEG4-biotin, PEG13, PEG25, PEG1K, PEG2K, PEG3.4K, PEG4K, PEG5K, IDA, ADA, Boc- Isophthalic acid, 1,3-phenylene diacetic acid, 1,4-phenylenediacetic acid, 1,2-phenylenediacetic acid, triazine, Boc-triazine, IDA-biotin, PEG4- biotin, AADA, , A heteroaromatic compound, and a polyethylene glycol-based linker having a molecular weight of about 400 Da to about 40,000 Da. Non-limiting examples of suitable linker moieties are shown in Table 2a below.

[Table 2a]

In some embodiments, the peptide dimer inhibitor is dimerized through a linker moiety. In some embodiments, the peptide dimer inhibitor is dimerized through intermolecular disulfide bonds formed between two cysteine residues, one on each monomer subunit. In some embodiments, a peptide dimer inhibitor is dimerized through both the intermolecular disulfide bond and the linker moiety formed between the two cysteine residues. In some embodiments, the intramolecular bond is a thioether, lactam, triazole, selenoether, diselenide or olefin instead of a disulfide bond.

An exemplary diagram of one embodiment of the dimer is shown below:

Those skilled in the art will appreciate that the linkers (e.g., C- and N-terminal linkers) moieties disclosed herein are non-limiting examples of suitable ones and that the present invention may include any suitable linker moiety. Accordingly, some embodiments of the invention include homologous or heterologous compositions consisting of two monomeric subunits selected from the peptides presented in any of the Tables herein, or comprising or consisting of sequences set forth in any of the Tables herein Dimer peptide inhibitor, wherein the C- or N-terminal (or internal amino acid residue) of each monomer subunit is joined by any suitable linker moiety to provide a dimeric peptide inhibitor with IL-23R inhibitory activity . In certain embodiments, the linker binds to the N- or C-terminus of one monomer subunit and the internal amino acid residue of the other monomer subunit constitutes a dimer. In certain embodiments, the linker binds to the internal amino acid residues of one monomer subunit and the internal amino acid residues of the other monomer subunit constitutes a dimer. In a further embodiment, the linker binds to the N- or C-terminus of the two subunits.

In certain embodiments, the peptide inhibitors of the present invention comprise two or more polypeptide sequences of the monomeric peptide inhibitors described herein.

In one embodiment, a peptide dimer inhibitor of the present invention comprises two peptide monomer subunits linked via one or more linker moieties, wherein each peptide monomer subunit contains 7 to 35 amino acid residues, A polynucleotide comprising at least 35 amino acid residues, 9 to 35 amino acid residues, 10 to 35 amino acid residues, 7 to 25 amino acid residues, 8 to 25 amino acid residues, 9 to 25 amino acid residues, 10 to 25 amino acid residues, Wherein the amino acid residue is selected from the group consisting of amino acid residues, 7 to 20 amino acid residues, 8 to 20 amino acid residues, 9 to 20 amino acid residues, 7 to 18 amino acid residues, 8 to 18 amino acid residues, 9 to 18 amino acid residues , Or 10 to 18 amino acid residues, or comprises the sequence of SEQ ID &lt; RTI ID = 0.0 &gt; Ia &lt; / RTI & The.

In certain embodiments, one or both of the monomer subunits comprises a sequence of any of SEQ ID NOS: X, I, II, III, IV or V as described herein.

In certain embodiments, the peptide dimer inhibitor comprises two peptide monomer subunits linked through one or more linker moieties, wherein each peptide monomer subunit is 8-20 amino acids in length and has the sequence disclosed herein For example, a sequence X, a sequence I, II, III, IV, or V. In certain embodiments, the peptide dimer inhibitor comprises two peptide monomer subunits linked via one or more linker moieties, wherein each peptide monomer subunit is 8-20 amino acids in length and has the sequence X, I, II, III, IV or V of SEQ ID NO.

In certain embodiments, the peptide dimer inhibitor, or a pharmaceutically acceptable salt or solvate thereof, has the structure of formula VI:

(R &lt; ^{1 &gt;} -XR &lt; ² &gt;) _2- L (VI)

Wherein each R ¹ is not present or independently, a bond (e.g., covalent bonds), or R ¹ is hydrogen, C1-C6 alkyl, C6-C12 aryl, C6-C12 aryl C1-C6 alkyl, C1-C20 Alkanoyl, and a PEGylated version of any of the foregoing, alone or as a spacer thereof;

Each R ² is absent independently, a bond (e.g., covalent bond), or is selected from OH or NH _2;

L is a linker moiety;

Each X is independently selected from the group consisting of 7 to 35 amino acid residues in length, 8 to 35 amino acid residues, 9 to 35 amino acid residues, 10 to 35 amino acid residues, 7 to 25 amino acid residues, Wherein the amino acid residues are selected from the group consisting of 25 amino acid residues, 9-25 amino acid residues, 10-25 amino acid residues, 7-20 amino acid residues, 8-20 amino acid residues, 9-20 amino acid residues, Amino acid residues, 8 to 18 amino acid residues, 9 to 18 amino acid residues, or 10 to 18 amino acid residues in length, each consisting of or consisting of peptide monomer subunits, Or comprises, a sequence of the sequence Ia as provided herein. In certain embodiments, each of the peptide monomer subunits comprises a sequence selected from the group consisting of SEQ ID NOS: Ix, Ia, Ib, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, , Or comprises or consists of a sequence of Ip, Iq, Iq ', Is, It, IIa, IIb, IIc, IId, IIIa, IIIb, IIIc, IIId, IIIe, IVa, IVb or Va-Vh.

In certain embodiments, one or both of the peptide monomer subunits of the peptide dimer inhibitor is, for example, cyclized via an intramolecular bond between X4 and X9. In certain embodiments wherein the peptide monomer subunit, both are cyclized, the intramolecular bond may be the same or different between the two peptide monomer subunits. In certain embodiments, one or both intramolecular bonds are disulfide bonds, thioether bonds, lactam bonds, selenoethers, diselenides, or olefinic bonds.

In one embodiment, X4 and X9 of one or both of the cyclized peptide monomer subunits are independently selected from Cys, Pen, hCys, D-Pen, D-Cys and D-hCys, Feed combination.

In one embodiment, X4 and X9 of one or both of the cyclized peptide monomer subunits are independently selected from the group consisting of Glu, Asp, Lys, Orn, Dap, Dab, D-Dap, D- Glu and D-Lys, and the intramolecular bond is a lactam bond.

In one embodiment, X4 and X9 of one or both of the cyclized peptide monomer subunits are each independently selected from? -Azido-Ala-OH, propargylicin, and the peptide dimer inhibitor comprises a triazole ring . In one embodiment, X4 and X9 of one or both of the cyclized peptide monomer subunits are each independently selected from the group consisting of 2-allyl glycine, 2- (3'-butenyl) glycine, 2- (4'- Glycine, 2- (5'-hexenyl) glycine, and the peptide dimer inhibitor is cyclized via ring close metathesis, thereby obtaining the corresponding olefin / 'stapled peptide'.

In one embodiment, X4 of one or both of the cyclized peptide monomer subunits is selected from the group consisting of 2-chloromethylbenzoic acid, methapto-propionic acid, methapto-butyric acid, 2-chloro-acetic acid, 3- X9 of one or both of the cyclized peptide monomer subunits is selected from the group consisting of hSer (Cl), Cys, Pen, hCys, D-Pen, D- Cys or D-hCys, and the intramolecular bond is a thioether bond.

In one embodiment, X4 of one or both of the cyclized peptide monomer subunits is selected from the group consisting of 2-chloromethylbenzoic acid, 2-chloro-acetic acid, 3-chloro-propionic acid, 4- chlorobutyric acid, , hSer (Cl), or Sec, and X9 of one or both of the cyclized peptide monomer subunits is hSer (Cl) or Sec and the intramolecular bond is a selenoether bond.

In certain embodiments, one or both of the intramolecular bonds are diselenide bonds.

In certain embodiments, one or both of the peptide monomer subunits are linear or noncircular.

In certain embodiments of the peptide dimer inhibitor, each X &lt; 7 &gt; and each X &lt; 11 &gt; In certain embodiments, each X7 and each X11 is both W, each X10 is Y, and each of X4 and X9 is both C. In certain embodiments, each X7 and each X11 is W, each X10 is Y, and each X4 and X9 is a thioether bond, a lactam bond, a triazole, a selenoether, a diselenide bond, or an olefin bond It is an amino acid that forms an intramolecular bond.

In certain embodiments of the peptide dimer inhibitor, one or both of the peptide monomer subunits may have a structure as set forth herein, e. G., In the following Tables 3a-3I, or as provided herein, Or wherein the peptide dimer inhibitor includes herein the amino acid sequences set forth in Table 3F, e.g., having the structure set forth in Table 3F below, or presented herein, for example, in Table 3F.

In certain embodiments, each R ¹ is independently a bond (e.g., a covalent bond) or is selected from the group consisting of hydrogen, C 1 -C 6 alkyl, C 6 -C 12 aryl, C 6 -C 12 aryl C 1 -C 6 alkyl, C 1 -C 20 alkanoyl, &Lt; / RTI &gt; or a spacer thereof. In certain embodiments, the N-terminus of each subunit is selected from the group consisting of hydrogen, C1-C6 alkyl, C6-C12 aryl, C6-C12 aryl, C1-C6 alkyl, C1-C20 alkanoyl, Is selected from those comprising alone or as a spacer thereof.

In certain embodiments of any of the peptide inhibitors having any of the various sequences set forth herein, each R ¹ (or N-terminal moiety) is independently selected from the group consisting of methyl, acetyl, formyl, benzoyl, trifluoroacetyl, iso Valeryl, isobutyryl, octanyl, and conjugated amides of lauric acid, hexadecanoic acid, and gamma-Glu-hexadecanoic acid.

In certain embodiments, each R ² (or C-terminal moiety) is independently a bond (e.g., a covalent bond) or is selected from OH or NH ₂ .

In certain embodiments of any of the peptide inhibitors having any of the various sequences set forth herein, each X is selected from the group consisting of 7 to 35 amino acid residues, 8 to 35 amino acid residues, 9 to 35 amino acid residues, Wherein the amino acid residue is selected from the group consisting of 10 to 35 amino acid residues, 7 to 25 amino acid residues, 8 to 25 amino acid residues, 9 to 25 amino acid residues, 10 to 25 amino acid residues, 7 to 18 amino acid residues, 8 To 18 amino acid residues, from 9 to 18 amino acid residues, or from 10 to 18 amino acid residues.

In certain embodiments, one or both Xs comprise, or alternatively consist of, any sequence of sequences as described herein. In certain embodiments of the peptide inhibitors, including dimers, or any of the sequences described herein, X does not include or does not comprise the amino acid sequence set forth in U.S. Patent Application Publication No. US2013 / 0029907. In certain embodiments of the peptide inhibitors, including dimers, or any of the formulas described herein, X does not include, or is not comprised of, the amino acid sequences set forth in U.S. Patent Application Publication No. US 2013/0172272.

In certain embodiments of the peptide inhibitors (monomers and dimers, both) of the invention comprising Cys at position X4 and Cys at position X9, the Cys at position X4 and the Cys at position X9 are connected by a disulfide bridge.

In certain embodiments of the peptide inhibitors of the present invention, each X &lt; 7 &gt; and each X &lt; 11 &gt;

In certain embodiments of the peptide inhibitors of the present invention, each X &lt; 7 &gt; and each X &lt; 11 &gt;

In certain embodiments of the peptide inhibitors of the present invention, each X7 and each X11 is both W, X10 is Y, and X4 and X9 are both C.

In certain embodiments, at least two of the cysteine residues of the peptide dimer inhibitor are linked by an intramolecular or intermolecular disulfide bridge.

In certain embodiments of any one monomer subunit or both, both present in a peptide dimer inhibitor (e.g., Ix, Ia-It, where allowed), X4 and X9 are both Cys.

In certain embodiments of any one monomer subunit present in the peptide dimer inhibitor, or both, (e.g., Ix, Ia-It, where allowed), X7 and X11 are both W.

X7 and X11 are both W, X10 is Y, and X4 and X9 (where &lt; RTI ID = 0.0 &gt; Are both Cys.

In certain embodiments of either one monomer subunit or both, which are present in the peptide dimer inhibitor (e.g., if allowed, Ia-It), X15 is GIy or Ser.

In certain embodiments of either monomeric subunit or both, which are present in the peptide dimer inhibitor (e.g., Ia-It, where allowed), X16 is AEA or AEP.

In certain embodiments of either monomeric subunit or both, which are present in the peptide dimer inhibitor (e.g., if allowed, Ia-It), X10 is Tyr or Phe, or an analogue of Tyr or Phe.

In certain embodiments of either monomeric subunit or both, present in a peptide dimer inhibitor (e.g., if allowed, Ia-It), X11 is Trp.

In certain embodiments of any of the peptide dimer inhibitors described herein, either or both of R &lt; ¹ &gt; are hydrogen.

In certain embodiments of the peptide dimer inhibitor of the present invention, the linker moiety (L) is any of the linkers described herein, or shown in Table 2A or 2B. In certain embodiments, L is a lysine linker, diethylene glycol linker, iminodiacetic acid (IDA) linker, beta -Ala-iminodiacetic acid (beta -Ala-IDA) linker, or PEG linker.

In various embodiments of any of the peptide dimer inhibitors, the peptide monomer subunit is attached to the linker moiety through its N-terminus, C-terminus, or internal amino acid residue, respectively.

In certain embodiments of any of the peptide dimer inhibitors, the N-terminus of each peptide monomer subunit is joined by a linker moiety.

In certain embodiments of any of the peptide dimer inhibitors, the C-terminus of each peptide monomer subunit is joined by a linker moiety.

In certain embodiments of any of the peptide dimer inhibitors, each peptide monomer subunit is joined by a linker moiety attached to an internal amino acid.

In certain embodiments of the peptide dimer inhibitor, the linker moiety is a diethylene glycol linker, an iminodiacetic acid (IDA) linker, a-Ala-iminodiacetic acid (beta -Ala-IDA) linker, or a PEG linker.

In certain embodiments of the peptide dimer inhibitor, one or both of the peptide monomer subunits have the structure shown in any of the Tables in the Examples, or include the amino acid sequence described in any of the Tables of the Examples.

In certain embodiments of the peptide inhibitors, including dimers, or any of the sequences described herein, X does not include or does not comprise the amino acid sequence set forth in U.S. Patent Application Publication No. US2013 / 0029907. In certain embodiments of the dimers, peptide inhibitors, or any of the sequences described herein, X does not comprise or is not comprised of the amino acid sequence set forth in U.S. Patent Application Publication No. US 2013/0172272 .

In certain embodiments of the peptide inhibitors of the present invention, each X7 and each X11 is both W, X10 is Y, and X4 and X9 are both Pen.

In certain embodiments, at least two of the cysteine residues of the peptide dimer inhibitor are linked by an intramolecular or intermolecular disulfide bridge.

Peptide inhibitor conjugates and biopolymers

In certain embodiments, the peptide inhibitors of the present invention, including both monomers and dimers, include one or more conjugated chemical substituents, such as lipophilic substituents and polymeric moieties, which are referred to herein as half-life extending moieties . Without wishing to be bound by any particular theory, it is believed that the lipophilic substituent enhances its half-life by protecting the peptide inhibitor from enzyme degradation by binding to albumin in the blood stream. In addition, polymer moieties are believed to enhance half-life and reduce elimination in the blood stream.

In further embodiments, any peptide inhibitor, e. G., A peptide of the sequence formulas (Va) to (Vh), may be attached to a linker moiety attached to an amino acid residue present in the inhibitor, e. G., The side chain of any amino acid of the peptide inhibitor To the N-terminal amino acid of the peptide inhibitor, or to the C-terminal amino acid of the peptide inhibitor.

In further embodiments, any of the peptide inhibitors, e. G., Peptides of the sequence formulas (Va) to (Vh), are conjugated to a half-life extending moiety attached to an amino acid residue present in the inhibitor, e. G., Any amino acid of a peptide inhibitor Terminal amino acid of the peptide inhibitor, or a half-life extension moiety that can be attached to the C-terminal amino acid of the peptide inhibitor.

In further embodiments, any peptide inhibitor, e. G., Peptides of the sequence formulas (Va) to (Vh), may be conjugated to a linker moiety attached to an amino acid residue present in the inhibitor such as a half-life extending moiety, Terminal amino acid of the peptide inhibitor, or a half-life extension moiety capable of binding to the linker moiety bound to the C-terminal amino acid of the peptide inhibitor.

In certain embodiments, the IL23R analog comprises a half-life extending moiety having the structure shown below wherein n = 0 to 24 or n = 14 to 24:

In certain embodiments, the IL23R analogs of the invention comprise the half-life extension moieties shown in Table 7.

[Table 7]

In certain embodiments, the half-life extending moiety is directly bound to the peptide inhibitor, while in other embodiments, the half-life extending moiety is attached to the peptide inhibitor via any linker moiety shown, for example, in Tables 6 or 8 .

[Table 8]

In certain embodiments, the peptide inhibitors of the present invention include any linker moiety shown in Table 8 and any half-life extending moiety shown in Table 7, including any of the following combinations shown in Table 9a.

[Table 9a]

In some embodiments, there may be multiple linkers present between the peptide and the conjugated moiety, e. G., The half-life extension moiety, as shown in Table 9b.

[Table 9b]

Exemplary exemplary peptide inhibitors of the invention, including peptide linkers with conjugate linkers and / or half-life extending moieties, are shown below. All amino acids are L amino acids unless otherwise indicated. The present invention also includes salt forms of any such peptide inhibitor, including, without limitation, its acetate salts.

Example 1 Synthesis of cyclo [[Abu] -QTWQC] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [ ₂

Example 1a Synthesis of Ac- [(D) -Arg] -cyclo [[Abu] -QTWQC] - [Phe [4- (2- aminoethoxy)] - [2- carboxy-tetrahydropyran] -ENN-NH ₂

Example 2 Preparation of Ac- [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] [Lys (Ac)] - NN -NH 2

Example 3 Synthesis of Cyclo [[Abu] -QTWQC] - [Phe [4- (2-aminoethoxy) - (Linker-half-life extension moiety)] - [2-Nal] -Tetrahydropyran] -ENN-NH2 &lt; / RTI _&gt;

Example 3a Synthesis of Ac- [(D) -Arg] Cyclo [[Abu] -QTWQC] - [Phe [4- (2- Aminoethoxy) - (Linker- half-life extension moiety)] - [2- - [4-amino-4-carboxy-tetrahydropyran] -ENN-NH ₂

Example 4: Synthesis of cyclo [[Abu] -QTWQC] - [Phe [4- (2-aminoethoxy)] - [2-Nal] Linker - half-life extension moiety)] - NN-NH ₂

Example 4a: Ac- [(D) -Arg] -cyclo [[Abu] -QTWQC] - [Phe [4- (2- aminoethoxy)] - [2- Carboxy-tetrahydropyran] - [Lys (linker-half-life extension moiety)] - NN-NH ₂

Example 5: Synthesis of cyclo [[Abu] -QTWQC] - [Phe [4- (2-aminoethoxy)] - [2-Nal] Lys (linker-half-life extending moiety)] - NH ₂

Example 5a Synthesis of Ac [(D) -Arg] -cyclo [[Abu] -QTWQC] - [Phe [4- (2-aminoethoxy)] - [2-Nal] -tetrahydropyran] -ENN- [Lys (linker-half-life extending moiety)] - NH ₂

Example 6: [Half life extending moiety-linker] - [Cyclo [[Abu] -QTWQC] - [Phe [4- (2- aminoethoxy)] - [2- carboxy-tetrahydropyran] -ENN-NH ₂

Example 6a: [Half-life extension moiety-linker] - [(D) -Arg] - [cyclo [[Abu] -QTWQC] - [Phe [4- (2-aminoethoxy)] - [2- - [4-amino-4-carboxy-tetrahydropyran] -ENN-NH ₂

Example 7: [Half-life extended moiety-linker] - [Pen] -NTWQ- [Pen] - [Phe [4- (aminoethoxy)] - [2-Nal] tetrahydropyran] - [Lys (Ac)] - NN-NH 2

Example 8: Ac- [Pen] -NTWQ- [Pen] - [Phe [4- (aminoethoxy)] - [2-Nal] - [ (Ac)] - NN- [Lys ( linker-half-life extending moiety)] - NH ₂

Example 9: Ac- [Pen] -NTWQ- [Pen] - [Phe [4- (aminoethoxy) - (linker-half-life extending moiety)] - [2- carboxy-tetrahydropyran] - [Lys (Ac)] - NN-NH 2

Example 10 Preparation of Ac- [Pen] -NTWQ- [Pen] - [Phe [4- (aminoethoxy)] - [2-Nal] - [ (linker-half-life extending moiety)] - NN-NH _2.

In certain embodiments, the half-life of a peptide inhibitor of the invention comprising a conjugated chemical substituent, such as a half-life extension moiety, is the same, but is at least 100%, at least 120%, at least 100% At least 150%, at least 200%, at least 250%, at least 300%, at least 400%, or at least 500%. In certain embodiments, lipophilic substituents and / or polymeric moieties increase the permeability of the peptide inhibitor through the epithelium and / or its residue in the mucosal membrane. In certain embodiments, the permeability through the epithelium through the epithelium of the peptide inhibitor of the invention comprising the conjugated chemical substituent and / or the residue of the peptidic inhibitor that does not contain a conjugated chemical substituent, At least 100%, at least 120%, at least 150%, at least 200%, at least 250%, at least 300%, at least 400%, or at least 500% of the half life.

In one embodiment, the side chains of one or more amino acid residues (e.g., Lys residues) of the peptide inhibitors of the invention are conjugated (eg, covalently attached) to a lipophilic substituent. The lipophilic substituent may be covalently bonded to an atom in the amino acid side chain or, alternatively, may be joined to the amino acid side chain via one or more spacers. The spacer, if present, can separate the peptide analog and the lipophilic substituent. In certain embodiments, the peptide inhibitor comprises any of the conjugated moieties set out in Tables 2-5.

In certain embodiments, the lipophilic substituent is a hydrocarbon chain having 4 to 30 C atoms, such as at least 8 or 12 C atoms, and preferably 24 or fewer C atoms, or 20 or fewer C atoms . &Lt; / RTI &gt; The hydrocarbon chain may be linear or branched and may be saturated or unsaturated. In certain embodiments, the hydrocarbon chain is replaced with a moiety that forms part of an attachment point to an amino acid side chain or spacer, e.g., an acyl group, a sulfonyl group, an N atom, an O atom, or an S atom. In some embodiments, the hydrocarbon chain is replaced with an acyl group, and thus the hydrocarbon chain may be substituted with an alkanoyl group, for example, a moiety such as palmitoyl, caproyl, lauroyl, myristoyl or stearoyl .

The lipophilic substituent may be attached to any amino acid side chain of the peptide inhibitor of the present invention. In certain embodiments, the amino acid side chain comprises a carboxy, hydroxyl, thiol, amide or amine group for forming esters, sulfonyl esters, thioesters, amides or sulfonamides comprising spacers or lipophilic substituents. For example, a lipophilic substituent may be attached to Asn, Asp, Glu, Gln, His, Lys, Arg, Ser, Thr, Tyr, Trp, Cys or Dbu, Dpr or Orn. In certain embodiments, the lipophilic substituent is conjugated to Lys. Amino acids presented as Lys in any of the sequences provided herein may be replaced by, for example, Dbu, Dpr or Orn, to which a lipophilic substituent has been added.

In certain embodiments, the peptide inhibitors of the present invention can be modified, for example, to enhance stability, increase permeability, or through the conjugation of chemical moieties to one or more amino acid side chains in the peptide to enhance drug- . For example, N (epsilon) of lysine N (epsilon),? -Carboxyl of aspartic acid, or? -Carboxyl of glutamic acid can be suitably functionalized. Thus, in order to prepare modified peptides, the amino acids in the peptides can be modified appropriately. In addition, in some cases, the side chain is selected from the group consisting of trifluoropentyl, acetyl, octanyl, butyl, pentyl, hexyl, palmityl, trifluoromethylbutyric acid, cyclopentanecarboxylic acid, cyclopropylacetic acid, Is acylated with an acylating organic compound selected from the group consisting of 4-fluorophenylacetic acid, 3-phenylpropionic acid, tetrahedra-2H-pyran-4-carboxylic acid, succinic acid glutaric acid or bile acid. For example, one of ordinary skill in the art will appreciate that a series of conjugates, such as, for example, PEG4, iso glu, and combinations thereof, may be linked. It will be appreciated by those skilled in the art that amino acids can be replaced by peptides in a co-hybrid fashion and Lys can be substituted, for example, in place of Dap, Dab, a-MeLys or Orn. Examples of modified residues in the peptides are shown in Table 1b below.

[Table 1b]

In a further embodiment of the present invention, alternatively or additionally, the side chains of one or more of the amino acid residues of the peptide inhibitor of the present invention may have, for example, a solubility and / or half life in vivo (e.g., in plasma), and / Is conjugated to the polymer moiety to increase bioavailability. Such modifications are also known to reduce the removal of therapeutic proteins and peptides (e. G., Renal clearance).

As used herein, "polyethylene glycol" or "PEG" is a polyether compound of the general formula H- (O-CH2-CH2) n-OH. PEG is also known as polyethylene oxide (PEO) or polyoxyethylene (POE) and, as used herein, PEO, PEE, or POG, depending on its molecular weight, means an oligomer or polymer of ethylene oxide. PEG refers to oligomers and polymers with molecular masses less than 20,000 Da, PEO refers to polymers with molecular masses above 20,000 Da, POE refers to polymers with any molecular mass Polymer. &Lt; / RTI &gt; PEG and PEO are liquid or low-melting solids, depending on their molecular weight. Throughout this disclosure, these three names are used in a way that is difficult to distinguish. PEG is prepared by polymerization of ethylene oxide and is commercially available over a wide range of molecular weights from 300 Da to 10,000,000 Da. PEG and PEO with different molecular weights appear to be usable in other applications and have different physical properties (e.g., viscosity) due to the chain length effect, but their chemical properties are almost the same. The polymer moiety is preferably water-soluble (amphipathic or hydrophilic), non-toxic, and pharmaceutically inert. Suitable polymer moieties include polyethylene glycol (PEG), a homo- or co-polymer of PEG, a monomethyl-substituted polymer of mPEG (mPEG), or polyoxyethylene glycerol (POG). See, for example, Int. J. Hematology 68: 1 (1998); [Bioconjugate Chem. 6: 150 (1995); And [Crit. Rev. Therap. Drug Carrier Sys. 9: 249 (1992). PEG used for the purpose of half-life extension, for example, 1 activated, alkoxy-terminated polyalkylene oxides (POA's) such as mono-methoxy-terminated polyethylene glycols (mPEG's); 2 activated polyethylene oxide (glycol) or other PEG derivatives, which is also contemplated. Suitable polymers will vary substantially by weight in the range of about 200 Da to about 40,000 Da, or for the purposes of the present invention, usually about 200 Da to about 60,000 Da are selected. In certain embodiments, a PEG having a molecular weight of 200 to 2,000, or 200 to 500 is used. Other types of PEG may also be used, depending on the initiator used in the polymerization process - typically a common initiator is a durable methyl ether PEG, or methoxypoly (ethylene glycol) (abbreviated as mPEG).

Low-molecular weight PEGs can also be used as pure oligomers, which are also referred to as being monodisperse, homogeneous, or separable. Which is used in certain embodiments of the present invention.

PEG is also available in other geometric forms: branched PEG has 3 to 10 PEG chains radiated from a central core group; Star PEG has 10 to 100 PEG chains that are radiated from a central core group; Comb PEG usually has multiple PEG chains grafted onto the polymer backbone. PEG can also be linear. The number often included in the name of PEG indicates its average molecular weight (e.g., PEG with n = 9 will have an average molecular weight of approximately 400 daltons and will be labeled with PEG 400).

As used herein, "PEGylation" is the process of covalently coupling a PEG structure to a peptide inhibitor of the invention, which is then referred to as a "PEGylated peptide inhibitor ". In certain embodiments, the PEG of the pegylated side chain is a PEG having a molecular weight of from about 200 to about 40,000. In certain embodiments, the PEG of the PEGylated spacer is selected from the group consisting of PEG3, PEG4, PEG5, PEG6, PEG7, PEG8, SEQ ID &lt; RTI ID = 0.0 &gt; , PEG 9, PEG 10, or PEG 11. In certain embodiments, the PEG of the PEGylated spacer is PEG 3 or PEG 8.

Other suitable polymeric moieties include poly-amino acids such as poly-lysine, poly-aspartic acid and poly-glutamic acid (see, e.g., Gombotz, et al. (1995), Bioconjugate Chem., Vol. 6: 332-351); and [Tsukada, et al. (1984), J. Natl. Cancer Inst., Vol. 73, pp. 721-729). The polymeric moiety may be linear or branched. In some embodiments, the molecular weight is 500-40,000 Da, such as 500-10,000 Da, 1,000-5,000 Da, 10,000-20,000 Da, or 20,000-40,000 Da.

In some embodiments, the peptide inhibitor of the present invention may comprise two or more of such polymeric moieties, in which case the molecular weight of all of the moieties will generally be included within the stated ranges.

In some embodiments, the polymer moiety is coupled (by covalent bond) to the amino, carboxyl, or thiol group of the amino acid side chain. Specific examples include the thiol group of the Cys residue and the epsilon amino group of the Lys residue, and the carboxyl group of the Asp and GIu residues may also be included.

Those skilled in the art will be familiar with suitable techniques that can be used to perform coupling reactions. For example, a PEG moiety containing a methoxy group may be coupled to a Cys thiol group by a maleimido linkage using a commercially available reagent from Nektar Therapeutics AL. For a detailed description of suitable chemical methods, see also WO 2008/101017, and the references cited above. The maleimide-functionalized PEG may also be conjugated to a side chain sulfhydryl group of the Cys residue.

As used herein, disulfide bond oxidation can be done in a single step, or a two step process. As used herein, in the case of a single oxidation step, a trityl protecting group is often used during assembly, whereby it can be deprotected during cleavage, followed by solution oxidation. If a second disulfide bond is required, it has the option of inherent or selective oxidation. In the case of selective oxidation requiring orthogonal protecting groups, Acm and trityl are used as protecting groups for cysteine. A protective cessation of the cysteine is removed, whereby the pair can be oxidized. A second oxidative deprotection step of the cysteine protected Acm group is carried out. In the case of intrinsic oxidation, a trityl protecting group is used for all cysteines, which allows natural folding of the peptides. Those skilled in the art will be familiar with suitable techniques that can be used to carry out the oxidation step.

A number of chemical moieties, including poly (ethylene) glycols, contain functional groups present in the 20 naturally occurring amino acids, such as the epsilon amino groups in lysine amino acid residues, thiols in cysteine amino acid residues, or other nucleophilic amino acid side chains Lt; / RTI &gt; When multiple naturally occurring amino acids are reacted in a peptide inhibitor, a number of isomers of the peptide, conjugated to one or more poly (ethylene) glycol strands at different positions within the peptide inhibitor through such non-specific chemical reactions Lt; RTI ID = 0.0 &gt; inhibitor. &Lt; / RTI &gt;

One advantage of certain embodiments of the present invention is that by chemical methods that are not reactive with the naturally occurring amino acids present in the peptide inhibitors, one or more non-natural amino acids (e. G. ) To introduce one or more chemical moieties (e. G., PEG). For example, azides and alkynyl groups are unreactive with all naturally occurring functional groups in the protein. Thus, non-natural amino acids can be introduced at one or more specific sites of the peptide inhibitor, where PEG or another modification without undesirable non-specific reactions is required. In certain embodiments, a certain covalent linkage between the PEG strand and the peptide inhibitor occurs over the course of a particular chemistry involved in the present reaction. In addition, the reaction may be carried out under mildly aqueous conditions that do not damage most peptides. In certain embodiments, the non-natural amino acid residue is AHA.

Chemical moieties attached to natural amino acids are limited in number and range. In contrast, chemical moieties attached to non-natural amino acids can use a significantly more useful chemistry to attach chemical moieties to the target molecule. In essence, non-natural amino acids, such as non-natural amino acids including reactive moieties or side chains to which attachment of a chemical moiety can be made, such as any protein including aldehyde or keto-derivatized amino acids Some of which may act as a substrate for attaching chemical moieties.

A number of chemical moieties may be attached or linked to a particular molecule through a variety of methods known in the art. A variety of such methods are described in U.S. Patent No. 8,568,706. As an illustrative example, an azide moiety may be useful to conjugate chemical moieties such as PEG or others described herein. Azide moieties act as reactive functional groups and are not present in most naturally occurring compounds (and thus are unreactive with the natural amino acids of naturally occurring compounds). Azides also undergo selective ligation with a limited number of reaction partners and azides are small and can be incorporated into biological samples without significantly altering the molecular size. One reaction that can incorporate or introduce an azide into a molecule is the copper-mediated Huisgen [3 + 2] cycloaddition of azide. This reaction can be used for selective PEGylation of peptide inhibitors (Tornoe et al., J. Org. Chem. 67: 3057, 2002); Rostovtsev et al., Angew. Chem., Int. Pp. 41: 596, 2002; and Wang et al., J. Am. Chem. Soc. 125: 3192, 2003, Speers et al., J. Am. Chem. Soc., 2003, 125, 4686).

Exemplary peptide inhibitors and peptides Dimer  Inhibitors, and methods for their preparation

Thus, the present invention provides various peptide inhibitors that bind to or associate with IL-23 to destroy or block the binding between IL-23 and IL-23R.

Exemplary peptide inhibitors and peptide dimer inhibitors of the present invention provide amino acid sequences of selected monomeric peptide inhibitors and peptide dimeric inhibitors and are shown in Tables 3a-3h, 4a, 4b , 5a-5c, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15. According to the protocol discussed herein, a number of peptide inhibitors and peptide dimer inhibitors as shown in the attached table were synthesized and cyclized. 23R to IL-23R, as described in the appended examples. TABLE-US-00003 TABLE 3 IL-23R IL-23R IL-23R IL-23R E3A E3H E4A E4B E5A E5C E6 E7 E8 E9 E10 E11 E12 E13 E- 23, or to inhibit IL-23 signaling (as measured by measuring changes in phospho-STAT 3 levels), as well as IC50 values of peptide dimeric inhibitors. Exemplary peptide inhibitors of the present invention are set forth in SEQ ID NO: (V), which provides the amino acid sequence of the selected peptide inhibitor, and in Tables 2-5. Such a peptide inhibitor is an acetate salt.

The peptide inhibitors of the present invention can be synthesized by a number of techniques known to those skilled in the art. In certain embodiments, monomer subunits are synthesized, refined, and dimerized using techniques described in the appended examples. In certain embodiments, the present invention encompasses any of the amino acid sequences described in SEQ ID NOS: I, II, III, IV, V or VI, or any of the tables herein, (Or a monomeric subunit thereof) comprising chemically synthesizing a peptide comprising, consisting of, or consisting essentially of, a peptide having an amino acid sequence. In another embodiment, the peptide is synthesized recombinantly, instead of being chemically synthesized. In certain embodiments, the peptide inhibitor is a dimer, the method comprises synthesizing both monomeric subunits of a peptide dimeric inhibitor, followed by dimerization of the two monomeric subunits to produce a peptide dimeric inhibitor . In various embodiments, dimerization is accomplished through any of the various methods described herein. In certain embodiments, a method of producing a peptide inhibitor (or a monomer subunit thereof) further comprises the step of cyclizing the peptide inhibitor (or a monomer subunit thereof) after its synthesis. In certain embodiments, cyclization is accomplished through any of the various methods described herein. In certain embodiments, the invention encompasses the use of the amino acid sequences described herein, including but not limited to SEQ ID NOS: I, II, III, IV, V or VI, or any of the accompanying embodiments, Comprising introducing an intramolecular bond, e.g., a disulfide, amide, or thioether bond, between two amino acid residues in a peptide comprising, consisting essentially of, or consisting essentially of a peptide having the amino acid sequence of SEQ ID NO: A peptide inhibitor (or a monomeric subunit thereof).

In a related embodiment, the invention comprises a polynucleotide encoding a polypeptide having the sequence set forth in any one of SEQ ID NOS: I, II, III, IV, V or VI, or any of the appended examples, table or sequence listing.

In addition, the invention includes vectors, such as expression vectors, wherein the invention comprises polynucleotides.

Treatment method

In certain embodiments, the invention includes a method of inhibiting IL-23 binding to IL-23R on a cell, comprising contacting IL-23 with a peptide inhibitor of the invention. In certain embodiments, the cell is a mammalian cell. In certain embodiments, the methods are performed in vitro or in vivo. Binding inhibition can be measured by a variety of conventional experimental methods and assays known in the art.

In an embodiment, the invention includes a method of inhibiting IL-23 signaling by a cell, comprising contacting IL-23 with a peptide inhibitor of the invention. In certain embodiments, the cell is a mammalian cell. In certain embodiments, the methods are performed in vitro or in vivo. In certain embodiments, inhibition of IL-23 signaling can be measured by measuring changes in the level of phospho-STAT3 in the cell.

In some embodiments, the invention provides a method of treating a condition associated with IL-21 or IL-23R (e.g., activation of the IL-23 / IL-23R signaling pathway), comprising administering a peptide inhibitor of the invention to a subject, A method of treating a subject suffering from an indication is provided. In one embodiment, an individual is administered an amount of the peptide inhibitor of the invention that is sufficient to inhibit (partially or completely) the binding of IL-23 to IL-23R in a subject, Or increased IL-23 or IL-23R activity or signal transduction in a subject suffering from a disease or condition. In certain embodiments, the inhibition of IL-23 binding to IL-23R is particularly effective in inhibiting the binding of IL-23R to an organ or tissue of a subject, such as the stomach, small intestine, large intestine / colon, intestinal mucosa, mucosal lamellar, pharyngeal, mesenteric lymph nodes, It happens.

In some embodiments, the methods of the invention comprise providing a peptide inhibitor of the invention to a subject in need thereof. In certain embodiments, the subject in need thereof is a subject who has been diagnosed with a disease or disorder associated with IL-23 / IL-23R, or is determined to be at risk for developing the disorder. In certain embodiments, the subject is a mammal.

In certain embodiments, the disease or disorder is selected from autoimmune inflammation and related diseases and disorders such as multiple sclerosis, asthma, rheumatoid arthritis, inflammatory bowel disease (IBD), pediatric IBD, juvenile IBD, Crohn's disease, sarcoidosis, Lupus, ankylosing spondylitis (condylar spondyloarthritis), psoriatic arthritis, or psoriasis. In certain embodiments, the disease or disorder is selected from the group consisting of psoriasis (e.g., psoriasis, psoriasis psoriasis, inverted psoriasis, pustular psoriasis, limbic pustular pustular pustular, psoriatic psoriasis or psoriatic psoriasis), atopic dermatitis, ectopic acne, Crohn &apos; s disease, Celiac disease (non-tropical sprue), bowel disease associated with serum-negative arthropathy, micro colitis, collagenous colitis, colitis associated with eosinophilic gastroenteritis / esophagitis, radiotherapy or chemotherapy, Colitis associated with congenital immunity such as in chronic granulomatous disease, glycogen accumulation type 1b, Hermansky-Puddlag syndrome, Chediak-Higashi syndrome, and Biscott-Aldrich syndrome, colitis caused by colonic resection and ileostomy, Gastrointestinal cancer, pancreatitis, insulin-dependent diabetes mellitus, mastitis, cholecystitis, cholangitis, primary biliary cirrhosis, viral related bowel disease, Jiyeom, and chronic sinusitis, asthma, uveitis, or graft-versus-host disease.

In certain related embodiments, the invention provides a method of treating a subject in need of selective inhibition of IL-23 or IL-23R signaling (or binding of IL-23 to IL-23R) 23 or IL-23R signaling (or binding of IL-23 to IL-23R) in the subject. In certain embodiments, the invention provides a method of treating a subject in need of selective inhibition of IL-23 or IL-23R signaling (or binding of IL-23 to IL-23R) 23 or IL-23R signaling (or binding of IL-23 to IL-23R) in the GI tract of said subject. In certain embodiments, the exposure of the administered peptide inhibitor in a GI tissue (e.g., the small intestine or colon) is at least 10-fold, at least 20-fold, at least 50-fold, or at least 100-fold greater than in blood exposure. In certain embodiments, the invention provides a method of treating a subject in need of selective inhibition of IL-23 or IL-23R signaling (or binding of IL-23 to IL-23R) Wherein the peptide inhibitor does not block the interaction between IL-6R and IL-6 or does not antagonize the IL-12 signaling pathway. Lt; RTI ID = 0.0 &gt; IL-23R &lt; / RTI &gt; signaling (or binding of IL-23 to IL-23R). In a further related embodiment, the invention provides a method of inhibiting GI inflammation and / or neutrophil infiltration into GI, comprising providing a subject inhibitor with a peptide inhibitor of the invention in need of inhibiting GI inflammation and / or neutrophil infiltration into GI . In some embodiments, the methods of the invention comprise the step of providing a subject in need thereof with a peptide inhibitor of the invention (i.e., a first therapeutic agent) in combination with a second therapeutic agent. In certain embodiments, the second therapeutic agent is provided to the subject prior to, and / or at the same time and / or subsequent to administration of the peptide inhibitor to the subject. In certain embodiments, the second therapeutic agent is an anti-inflammatory agent. In certain embodiments, the second therapeutic agent is a non-steroidal anti-inflammatory drug, a steroid agent, or an immunomodulator. In another embodiment, the method comprises administering a third therapeutic agent to a subject. In certain embodiments, the second therapeutic agent is an antibody that binds to IL-23 or IL-23R.

In certain embodiments, a pharmaceutical composition comprising a peptide inhibitor, or a peptide inhibitor, is suspended in the delayed-release matrix. As used herein, a sustained release matrix is a matrix made of a substance, usually a polymer, that can be degraded by enzymatic or acid-basic hydrolysis or by dissolution. Once inserted into the body, this matrix is acted upon by enzymes and body fluids. The sustained release matrix is preferably a biocompatible material, such as a liposome, a polylactide (polylactic acid), a polyglycolide (a polymer of glycolic acid), a polylactideco-glycolide (a copolymer of lactic acid and glycolic acid) The present invention relates to a pharmaceutical composition comprising at least one compound selected from the group consisting of hydrides, poly (ortho) esters, polypeptides, hyaluronic acid, collagen, chondroitin sulfate, carboxylic acid, fatty acid, phospholipid, polysaccharide, nucleic acid, polyamino acid, amino acid such as phenylalanine, tyrosine, isoleucine, polynucleotide , Polyvinylpyrrolidone, and silicone. One embodiment of the biodegradable matrix is a matrix consisting of one of polylactide, polyglycolide, or polylactide co-glycolide (a copolymer of lactic acid and glycolic acid).

In certain embodiments, the invention includes a pharmaceutical composition comprising one or more peptide inhibitors of the invention and a pharmaceutically acceptable carrier, diluent or excipient. A pharmaceutically acceptable carrier, diluent or excipient refers to a non-toxic solid, semi-solid or liquid filler, diluent, encapsulating material or formulation auxiliary of any type. By including various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol sorbic acid and the like, microbial action can be prevented. It may also be desirable to include isotonic agents, such as sugars, sodium chloride, and the like.

In certain embodiments, the compositions are administered orally, parenterally, intracisternally, intravaginally, intraperitoneally, rectally, topically (by powder, ointment, drip, suppository or transdermal patches) (E. G., A non-particulate spray), into the eye (e. G., Into the eye), or buccally. As used herein, the term "parenteral" refers to a mode of administration including intravenous, intramuscular, intraperitoneal, intrasternal, subcutaneous, intradermal and intraarticular administration and infusion. Thus, in certain embodiments, the composition is formulated for delivery by any of the above routes of administration.

In certain embodiments, the parenterally injectable pharmaceutical composition comprises a pharmaceutically acceptable sterile aqueous or nonaqueous solution, dispersion, suspension or emulsion, or sterile powders that are reconstituted with a sterile injectable solution or dispersion just prior to use. Examples of suitable aqueous or nonaqueous carriers, diluents, solvents or vehicles include water, ethanol, an oleanol such as glycerol, propylene glycol, polyethylene glycol, etc., carboxymethylcellulose and suitable mixtures thereof, beta -cyclodextrin, For example, olive oil), and injectable organic esters such as ethyl oleate. Proper fluidity can be maintained, for example, by using coating materials, such as lecithin, in the case of dispersions, by maintaining the required particle size, and by using surfactants. These compositions may also contain adjuvants such as preserving agents, wetting agents, emulsifying agents, and dispersing agents. The absorption of the injectable pharmaceutical form may be extended by including agents that delay absorption, for example, aluminum monostearate and gelatin.

A commonly used depot form is a microcapsule matrix of a peptide inhibitor in one or more biodegradable polymers such as polylactide-polyglycolide, poly (orthoester), poly (anhydride), and (poly) &Lt; / RTI &gt; Depending on the ratio of peptide to polymer and the nature of the particular polymer used, the rate of peptide inhibitor can be controlled. Injectable depot preparations are also prepared by entrapping peptide inhibitors in liposomes or microemulsions that are compatible with body tissues.

The injectable preparation may be sterilized, for example, by filtration through a bacteria-retaining filter, or by introducing the sterilizing agent in the form of a sterile solid composition that may be dissolved or dispersed in sterile water or other sterile injectable medium immediately prior to use. .

Topical administration includes administration to the skin or mucosa, including the surface of the lungs and eyes. Compositions for local pulmonary administration, including inhalation and non-osmotic compositions, may include solutions and suspensions in aqueous and non-aqueous formulations, which may be prepared as dry powders which may be compressed or uncompressed. In the non-compressible powder composition, the active ingredient, which may be in finely divided form, may be, for example, a mixture mixed with a larger pharmaceutically acceptable inert carrier, including particles having a size of up to 100 [mu] m in diameter Can be used. Suitable inert carriers include sugars, such as lactose.

Alternatively, the composition may be compressible and contain a compressed gas, such as nitrogen or a liquefied gas propellant. The liquefied propellant medium and in fact the entire composition can ensure that the active ingredient is not dissolved therein to any substantial extent. The compressible composition may also include a surface active agent, such as a liquid or solid non-ionic surface active agent, or it may be a solid anionic surface active agent. It is preferred to use a solid anionic surfactant in the form of a sodium salt.

Additional topical dosage forms are those administered by the eye. The peptide inhibitors of the present invention allow the peptide inhibitor to penetrate into the cornea and interior regions of the eye such as anterior, posterior, vitreous, retentate, vitreous humor, cornea, iris / eyelash, lens, choroid / retina and sclera , The peptide inhibitor may be delivered in a pharmaceutically acceptable ocular vehicle. A pharmaceutically acceptable ocular vehicle may be, for example, ointment, vegetable oil or an encapsulating material. Alternatively, the peptide inhibitors of the present invention can be injected directly into the body fluids and the feed liquid.

Compositions for rectal or vaginal administration are suitable non-irritating excipients, or carriers, which are solid at room temperature but liquid at body temperature, and therefore are melted in the rectum or vaginal cavity and release the active compound, Such as, for example, cocoa butter, polyethylene glycol or suppository waxes.

The peptide inhibitors of the present invention may also be administered in the form of liposomes or other lipid-based carriers. As is known in the art, liposomes are generally derived from phospholipids or other lipid materials. Liposomes are formed by hydrated liquid crystals of single or multi-layered structure dispersed in a water-soluble medium. Any non-toxic, physiologically acceptable, metabolizable lipids capable of forming liposomes can be used. The present composition in liposomal form may contain, in addition to the peptide inhibitors of the present invention, stabilizers, preservatives, excipients and the like. In certain embodiments, the lipid comprises both natural and synthetic phospholipids, including phosphatidyl choline (lecithin) and serine. Methods for forming liposomes are known in the art.

Pharmaceutical compositions intended for use in the present invention which are suitable for parenteral administration include sterile aqueous solutions of peptide inhibitors and / or aqueous sterile solutions which are made to be isotonic with the blood of the recipient, generally using sodium chloride, glycerin, glucose, mannitol, sorbitol, Aqueous suspensions.

In some aspects, the invention provides a pharmaceutical composition for oral delivery. The compositions and peptide inhibitors of the present invention may be formulated for oral administration according to the methods, techniques, and / or delivery vehicles described herein. In addition, the peptide inhibitors of the present invention may be modified or incorporated into systems or delivery vehicles that are not well known in the art, but are well known in the art and suitable for use for oral delivery of peptides It will be understood by those skilled in the art.

In certain embodiments, formulations for oral administration comprise adjuvants (e. G., Resorcinol and / or nonionic surfactants such as polyoxyethylene oleyl ether and n-hexadecyl polyethylene &lt; RTI ID = (E. G., A pancreatic trypsin inhibitor, diisopropyl fluorophosphate (DFF) or tracylol) to inhibit enzymatic degradation. In certain embodiments, the peptide inhibitor of solid dosage form for oral administration comprises at least one additive such as sucrose, lactose, cellulose, mannitol, trehalose, raffinose, maltitol, dextran, starch, agar, alginate, chitin, Chitosan, pectin, tragacanth gum, gum arabic, gelatin, collagen, casein, albumin, synthetic or semi-synthetic polymers, or glycerides. The dosage forms may also contain other types of additives such as inert diluents, lubricants such as magnesium stearate, parabens, preservatives such as sorbic acid, ascorbic acid, alpha-tocopherol, antioxidants such as cysteine, Release agents, binders, thickeners, buffering agents, pH adjusting agents, sweeteners, flavoring agents or fragrances.

In certain embodiments, suitable oral dosage forms or unit dosage forms for use with the peptide inhibitors of the present invention include peptide inhibitors and mixtures of non-drug ingredients or excipients, as well as other non-recyclable materials . &Lt; / RTI &gt; Oral compositions may include at least one of liquid, solid, and semi-solid dosage forms. In some embodiments, an oral dosage form comprising an effective amount of a peptide inhibitor, wherein the dosage form is an oral dosage form comprising at least one of a pill, tablet, capsule, gel, paste, drink, syrup, ointment, Lt; / RTI &gt; In some cases, provided are oral dosage forms designed and configured to delay the release of a peptide inhibitor in the small intestine and / or colon of the subject.

In one embodiment, an oral pharmaceutical composition comprising a peptide inhibitor of the invention comprises an enteric coating designed to delay the release of a peptide inhibitor in the small intestine. In at least some embodiments, there is provided a pharmaceutical composition comprising a peptide inhibitor of the invention and a protease inhibitor, such as aprotinin, in a delayed release pharmaceutical formulation. In some embodiments, the pharmaceutical compositions of the present invention comprise an enteric coat that is soluble in gastric juice at a pH of at least about pH 5.0. In at least one embodiment, polymers comprising dissociative carboxyl groups, such as hydroxypropylmethylcellulose phthalate, cellulose acetate phthalate and cellulose acetate trimellitate, derivatives of cellulose, and similar derivatives of cellulose and other carbohydrate polymers Lt; RTI ID = 0.0 &gt; a &lt; / RTI &gt; enteric coating.

In one embodiment, a pharmaceutical composition comprising a peptide inhibitor of the present invention is intended to be administered to a enteric coating that is designed to protect and release the pharmaceutical composition in a controlled manner within the lower gastrointestinal tract of the subject, and to prevent systemic side effects / RTI &gt; In addition to intestinal coatings, the peptide inhibitors of the present invention may be encapsulated, coated, engaged, or otherwise associated within any suitable oral drug delivery system or component. For example, in some embodiments, the peptide inhibitors of the present invention are provided in a lipid carrier system comprising at least one of a polymeric hydrogel, nanoparticles, microspheres, micelles, and other lipid systems.

To overcome peptide degradation in the small intestine, some embodiments of the invention include a hydrogel polymeric carrier system comprising a peptide inhibitor of the invention, whereby the hydrogel polymer is capable of degrading the protein in the small intestine and / Lt; / RTI &gt; The peptide inhibitors of the present invention may be further formulated so that they can be used in applications that are compatible with carrier systems designed to increase the dissolution kinetics of peptides and enhance intestinal absorption. The methods include using liposomes, micelles, and nanoparticles to increase GI tract permeability of the peptides.

A variety of bioreactive systems may also be combined with one or more of the peptide inhibitors of the present invention to provide pharmaceutical formulations for oral delivery. In some embodiments, the peptide inhibitors of the present invention may be combined with a mucoadhesive polymer (e. G., PEG, poly (methacrylic acid) [PMAA]) with bioreactive systems such as hydrogels and hydrogen bonding groups to provide therapeutic agents for oral administration. , Cellulose, Eudragit (R), chitosan and alginate). Another embodiment is to optimize the drug retention time for the peptide inhibitors disclosed herein wherein the surface of the peptide inhibitor surface is modified to include mucoadhesive properties through hydrogen bonding, polymers with attached mucin and / or hydrophobic interactions , &Lt; / RTI &gt; The modified peptide molecule may exhibit extended drug retention times within the subject depending on the desired characteristics of the present invention. In addition, the targeted mucoadhesive system can specifically bind to receptors on intestinal and M-cell surfaces, thereby further increasing absorption of particles comprising a peptide inhibitor.

Another embodiment provides a method of orally delivering a peptide inhibitor of the present invention, wherein the peptide inhibitor is provided in combination with a permeation enhancer that promotes peptide transport through the intestinal mucosa by increasing intercellular or cross- &Lt; / RTI &gt; Various permeation enhancers and methods for oral delivery of therapeutic agents have been described by Brayden, D.J., Mrsny, R.J., 2011. Oral peptide delivery: prioritizing the leading technologies. Ther. Delivery 2 (12), 1567-1573.

In certain embodiments, the pharmaceutical compositions and formulations of the present invention comprise a peptide inhibitor of the invention and one or more permeation enhancers. Examples of absorption enhancers include, for example, bile acids, fatty acids, surfactants (anionic, cationic and non-anionic), chelators, Zonular OT, esters, cyclodextrins, dextran sulfate, azone, Ether, EDTA, sucrose ester, and phosphatidylcholine. Absorption enhancers are typically not carriers themselves, but they are also extensively associated with other carriers for improving oral bioavailability by transporting peptides and proteins across the intestinal mucosa. Such materials may be added to the formulation as an excipient or incorporated to form a nonspecific interaction with the intended peptide inhibitor.

(GRAS) dietary ingredients and / or other naturally occurring substances that have been found to promote close contact permeation include, for example, asglycerides, acylcarnitines, bile salts, and heavy chain fatty acids do. It has been proposed that the sodium salt of the heavy chain fatty acid (MCFAS) is also a permeation enhancer. The most widely studied MCFAS is the sodium caprate, a salt of capric acid, which contains 2 to 3% fatty acids in the milk fat fraction. To date, sodium caprate has been used predominantly as an excipient in the suppository formulation for the rectal ampicillin absorption (Doktacillin (TM)). The permeability characteristics of another dietary MCFAS, sodium caprylate (8-carbon), were lower in vitro than sodium caprate. Sodium caprylate and peptidic drugs are formulated in mixtures with other excipients in oils to produce oily suspensions (OS) that enhance permeability (Tuvia, S. et al., Pharmaceutical Research, Vol. 31, No. 8 , pp. 2010-2021 (2014).

For example, in one embodiment, a permeation enhancer is combined with a peptide inhibitor, wherein the permeation enhancer comprises at least one of a heavy chain fatty acid, a long chain fatty acid, a bile acid salt, an amphoteric surfactant, and a chelating agent. In certain embodiments, the heavy chain fatty acid salt promotes absorption by increasing intracellular permeability of the intestinal epithelium. In one embodiment, a permeation enhancer comprising sodium N- [hydroxybenzoyl) amino] caprylate is used to form a weak noncovalent association with a peptide inhibitor of the present invention, wherein the permeation enhancer assists membrane transport, Once it reaches the blood circulation, it helps to further dissociate. In another embodiment, a peptide inhibitor of the invention is conjugated to oligoarginine, whereby cell penetration into various cell types of the peptide is increased. Additionally, in at least one embodiment, a non-covalent bond is provided between a peptide inhibitor of the invention and a permeation enhancer selected from the group consisting of cyclodextrins (CD) and dendrimers, wherein the permeation enhancer reduces peptide aggregation, And increases stability and solubility to peptide inhibitor molecules.

In certain embodiments, the pharmaceutical composition or formulation comprises a peptide inhibitor of the invention and a transient permeability enhancer (TPE). Permeation enhancers and TPE may be used to increase oral bioavailability or peptide inhibitors. An example of a TPE that can be used is an oil suspension formulation that disperses the powder and therapeutic agent containing sodium caprylate (Tuvia, S. et al., Pharmaceutical Research, Vol. 31, No. 8, pp. 2010-2021 2014).

In certain embodiments, pharmaceutical compositions and formulations may comprise a peptide inhibitor of the invention and one or more absorption enhancers, enzyme inhibitors or mucoadhesive polymers.

In certain embodiments, the peptide inhibitors of the present invention are formulated in a pharmaceutical vehicle, such as an emulsion, liposome, microspheres or nanoparticles.

Another embodiment of the invention provides a method of treating a subject using a peptide inhibitor of the invention with increased half-life. In one aspect, the invention provides a pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein the half-life is from several hours to several hours, in vitro or in vivo (e.g., when administered to a human subject) sufficient to administer a therapeutically effective amount daily (qd) RTI ID = 0.0 &gt; 1 &lt; / RTI &gt; In another embodiment, the half-life of the peptide inhibitor is at least 3 days, sufficient to administer a therapeutically effective amount every week (q.w.). Additionally, in another embodiment, the half-life of the peptide inhibitor is at least 8 days, sufficient to provide a therapeutically effective dose every other week (bi.w.) or monthly. In another embodiment, the peptide inhibitor is derivatized or modified to have an extended half-life as compared to a non-derivatized or unmodified peptide inhibitor. In another embodiment, the peptide inhibitor comprises one or more chemical modifications to prolong serum half-life.

When used in at least one of the treatment or delivery systems described herein, the peptide inhibitors of the present invention may be used in pure form or, if present in such form, be used in the form of a pharmaceutically acceptable salt.

The total daily dosage of the peptide inhibitors and compositions of the present invention may be determined by the attending physician within the scope of sound medical judgment. The specific therapeutically effective dose level for any particular subject will depend on a) the severity of the disorder and disorder being treated; b) the activity of the particular compound used; c) the particular composition employed, the age, weight, general health status, sex and feeding of the patient; d) the time of administration, route of administration, and rate of release of the particular peptide inhibitor used; e) duration of treatment; f) a drug used together or concurrently in combination with the particular peptide inhibitor used; And similar factors well known in the medical arts.

In certain embodiments, the total daily dose of a peptide inhibitor of the present invention to be administered to a human or other mammalian host in a single dose or sub-dose is, for example, from 0.0001 to 300 mg / kg (body weight) / day or 1 To 300 mg / kg (body weight) / day.

Noninvasive detection of intestinal inflammation

The peptide inhibitors of the present invention can be used to detect, evaluate and diagnose intestinal inflammation by micro PET imaging, wherein the peptide inhibitor is labeled with a chelating group or a detectable label as part of a non-invasive diagnostic method. In one embodiment, the peptide inhibitor is conjugated to a bifunctional chelator. In another embodiment, the peptide inhibitor is radiolabeled. The labeled peptide inhibitor is then administered to the subject, either orally or rectally. In one embodiment, the labeled peptide inhibitor is included in drinking water. After ingestion of the peptide inhibitor, micro PET imaging can be used to visualize inflammation throughout the intestinal tract and gastrointestinal tract of the subject.

IL-23 signaling Inhibitory  Identification of Peptide Inhibitors

As described herein, in certain embodiments, the peptide inhibitors of the invention preferentially bind to human IL-23R and / or rat IL-23R as compared to murine IL-23R. In comparison to human IL-23R or rat IL-23R, mouse IL-23R is associated with a region corresponding to about amino acid residue 315 to about amino acid residue 340 of the murine IL-23R protein, such as the amino acid region NWQPWSSPFVHQTSQETGKR Contains additional amino acids. In certain embodiments, the peptide inhibitor binds to the region of human IL-23R from about amino acid 230 to about amino acid residue 370.

The present invention identifies inhibitors of IL-23R (e. G., Peptide inhibitors) based on identifying agents (e. G., Peptides) that preferentially bind to human IL-23R or rat IL-23R relative to mouse IL- Lt; / RTI &gt; In certain embodiments, the method comprises: (a) determining the amount of a candidate agent that binds to a human IL-23R polypeptide or a rat IL-23R polypeptide; (b) determining the amount of a candidate agent that binds to the murine IL-23R polypeptide; 23R polypeptide or rat IL-23R polypeptide, and (c) comparing a measure of an amount binding to a human IL-23R polypeptide or a rat IL-23R polypeptide to a measure of an amount binding to a mouse IL-23R polypeptide, 23R polypeptide is greater than the amount that binds to the murine IL-23R polypeptide, wherein the candidate compound is an inhibitor of IL-23R. In certain embodiments, the measurement of the amount of binding to human IL-23R polypeptide or rat IL-23R polypeptide is at least 1.5 times, at least 2 times, at least 3 times, at least 4 times , At least 5 times, at least 10 times, at least 20 times, at least 30 times, at least 40 times, at least 50 times, at least 100 times, at least 200 times, at least 500 times, or at least 100 times greater, 23R. &Lt; / RTI &gt; In certain embodiments, the candidate compound is a peptide. In certain embodiments, the peptides are peptides of one of the sequences described herein. In certain embodiments, the human IL-23 polypeptide or the rat IL-23R polypeptide comprises or consists of the full-length human IL-23R or rat IL-23R protein, respectively. In another embodiment, the human IL-23R polypeptide is a fragment of a full-length human IL-23R protein comprising at least eight amino acid residues within the region of human IL-23R at about amino acid residue 230 to about amino acid residue 370. In another embodiment, the rat IL-23R polypeptide is a fragment of a full-length rat IL-23R protein comprising at least 8 amino acid residues within the region of rat IL-23R from about 245 amino acid residues to about 385 amino acid residues.

In another embodiment, the invention provides for the use of a compound of formula (I) wherein the additional amino acid is present in the murine IL-23R protein from about amino acid residue 315 to about amino acid residue 340, such as the amino acid region NWQPWSSPFVHQTSQETGKR (E.g., a peptide inhibitor) of IL-23R based on identifying an agent that binds to the region of human IL-23R or rat IL-23 that is destroyed. In certain embodiments, the method comprises (a) contacting a fragment of a human IL-23R polypeptide contained within about 230 amino acid residues to about 370 amino acid residues, or a fragment of a rat IL-23R polypeptide comprised within about amino acid residue 245 to about amino acid residue 385 Measuring the amount of candidate agent binding to the fragment; (b) determining the amount of a candidate agent that binds to a negative control (e. g., a negative control peptide not associated with human IL-23R or rat IL-23R); And (c) comparing the amount of a fragment of a human IL-23R polypeptide, or a fragment thereof, to a fragment of a rat IL-23R polypeptide, to a negative control, wherein the human IL-23R polypeptide fragment or Wherein the candidate compound is an inhibitor of IL-23R if the measure of the amount binding to the rat IL-23R polypeptide fragment is greater than the amount binding to the negative control. In certain embodiments, a measurement of the amount of binding to human IL-23R polypeptide fragment or rat IL-23R polypeptide fragment is at least 1.5 times, at least 2 times, at least 3 times, at least 4 times, At least 5 times, at least 10 times, at least 20 times, at least 30 times, at least 40 times, at least 50 times, at least 100 times, at least 200 times, at least 500 times, or at least 100 times greater, . &Lt; / RTI &gt; In certain embodiments, the candidate compound is a peptide. In certain embodiments, a fragment of human IL-23R has at least 8, at least 12, at least 20, at least 50, or at least 100, Or amino acid residues. In another embodiment, a fragment of a rat IL-23R polypeptide comprises at least 8, at least 12, at least 20, at least 50, or at least 100 of the amino acid residues 245 to about 385 in the region of the rat IL-23R , Or both amino acid residues.

Methods for determining binding of a candidate compound to an IL-23 polypeptide are well known in the art and include, but are not limited to, in vitro and cell-based binding assays, including those described herein. For example, candidate compounds labeled for a sufficient time and under such conditions to allow binding to occur can be incubated with the recombinantly produced IL-23R polypeptide or negative control conjugated to a solid support, followed by binding RTI ID = 0.0 &gt; IL-23R &lt; / RTI &gt; polypeptide.

Noninvasive detection of intestinal inflammation

The peptide inhibitors of the present invention can be used to detect, evaluate and diagnose intestinal inflammation by micro PET imaging, wherein the peptide inhibitor is labeled with a chelating group or a detectable label as part of a non-invasive diagnostic method. In one embodiment, the peptide inhibitor is conjugated to a bifunctional chelator. In another embodiment, the peptide inhibitor is radiolabeled. The labeled peptide inhibitor is then administered to the subject, either orally or rectally. In one embodiment, the labeled peptide inhibitor is included in drinking water. After ingestion of the peptide inhibitor, micro PET imaging can be used to visualize inflammation throughout the intestinal tract and gastrointestinal tract of the subject.

IBD  An animal model sick

The invention encompasses animal models that suffer from a disease, including inflammatory diseases and disorders, such as inflammatory bowel disease, such as Crohn's disease and colitis. As described in the appended examples, several animal models with inflammatory diseases and disorders have been developed.

In one embodiment,

(a) providing dextran sulfate sodium (DSS) to a rat in an amount sufficient to elicit IBD;

(b) providing the rat with a predetermined amount of the candidate compound; And

(c) measuring the amount of IBD symptoms present in the rat after providing the DSS and the candidate compound,

Wherein a predetermined amount of the IBD symptoms measured in (c) is less than the amount measured in the control rat (e. G., The vehicle control) receiving the positive amount of DSS, receiving a certain amount of the control compound, or not receiving the peptide , The candidate compound inhibits or reduces an inflammatory disease or disorder, the method comprising evaluating the ability of the candidate compound to inhibit or reduce the inflammatory disease disorder .

In certain embodiments, the rats are provided with DSS for about 5 to 12 days, such as about 9 days. In certain embodiments, the rats are provided with DSS by exposing the rats unrestrictedly to drinking water containing DSS, such as about 1% to about 10% DSS, about 2% to about 5% DSS, or about 3% DSS. In certain embodiments, the rats are provided with a test compound at about 5 mg / kg to about 100 mg / kg, or about 10 mg / kg to about 50 mg / kg, or about 20 mg / kg or about 30 mg / kg . In certain embodiments, the rats are orally provided, for example, with test compounds in drinking water. In certain embodiments, the DSS assay is performed as described in the appended examples.

In another embodiment,

(a) providing 2,4,6-trinitrobenzenesulfonic acid (TNBS) to rats in an amount sufficient to induce IBD;

(b) providing the rat with a predetermined amount of the candidate compound; And

(c) measuring the amount of IBD symptoms present in the rat after providing TNBS and the candidate compound,

Wherein the amount of IBD symptoms measured in (c) is less than the amount measured in a control rat (e.g., a vehicle control) that has received the positive amount of TNBS, has received an amount of a control compound, or has not received a peptide , The candidate compound inhibits or reduces an inflammatory disease or disorder, the method comprising evaluating the ability of the candidate compound to inhibit or reduce the inflammatory disease disorder .

In certain embodiments, the animal is administered at a dose of about 10 mg / kg to about 200 mg / kg, such as about 10 mg / kg, about 20 mg / kg, about 30 mg / kg, about 40 mg / About 60 mg / kg, about 70 mg / kg, about 80 mg / kg, about 90 mg / kg, about 100 mg / kg, about 120 mg / kg, about 150 mg / kg or about 200 mg / . In certain embodiments, TNBS is present in an alcohol, such as 45% -50% ethanol. In certain embodiments, the TNBS is administered rectally. In certain embodiments, the rats are provided with a test compound at about 5 mg / kg to about 100 mg / kg, or about 10 mg / kg to about 50 mg / kg, or about 20 mg / kg or about 30 mg / kg . In certain embodiments, the rats are orally provided, for example, with test compounds in drinking water. In certain embodiments, the TNBS assay is performed as described in the appended examples.

In certain embodiments, the IBD symptom is present immediately after, or at a later time, for example, DSS or TNBS and a candidate compound provided (or a test compound provided) Or no compound is provided) at about 3 days, 5 days, or 9 days. In certain embodiments, the IBD symptoms to be measured include at least one of weight loss rate (%), stool hardness, a quantitative hangover score, and a ratio of colon weight to colon length. In certain embodiments, the IBD symptoms are measured using a Disease Activity Index (DAI) score and / or a ratio of colon weight to colon length, wherein the DAI score is weight loss rate (%), stool grade, and quantitative occlusion score And evaluation from three parameters, and can achieve a maximum value of three units.

In certain embodiments, neutralizing anti-IL-23p19 antibodies are used as a comparative or positive control.

In certain embodiments, to assess the degree of inflammatory response, the animals are observed daily, for example, for weight loss rate (%) and dilatation or diarrhea signs. Rats were sacrificed after a period of time (e. G., 5, 6 or 7 days) after DSS or TNBS inoculation and the total length of the colon and colonic weight from cecum to rectum were recorded. Colitis severity can be assessed by a pathologist blinded to the treatment identity. In addition to the thickness of the colon wall, the colon damage could be assessed visually based on the 0-4 scale according to Table 19 below and histopathological scores were measured based on the following parameters (Tables 20 and 21 below).

In certain embodiments, the IBD symptoms are measured in three groups of rats, each comprising at least three animals, such as six animals each, wherein the three groups are selected from the group of vehicles, DSS or TNBS, And a DSS or TNBS group using a control (e.g., administering PO at 100 mg / kg of sulfasalazine, QD).

Example

Example 1

Peptide monomer synthesis

Using Merrifield solid phase synthesis technology, Protein Technology ' s Symphony &lt; RTI ID = 0.0 &gt; Peptide monomers were synthesized. The peptide is assembled using HBTU (O-benzotriazole-N, N, N ', N'-tetramethyl-uronium-hexafluoro-phosphate), diisopropylethylamine (DIEA) Respectively. For some amino acid coupling, PyAOP (7-azabenzotriazol-1-yloxy) tripyrrolidinophosphonium hexafluorophosphate) and DIEA conditions were used. In the case of a peptide containing C-terminal amide, Rink Amide MBHA resin (100-200 mesh, 0.57 mmol / g) was used and in the case of a peptide having C-terminal acid, N-α-Fmoc protection Gt; Wang &lt; / RTI &gt; Coupling reagents (premixed HBTU and DIEA) were prepared at a concentration of 100 mmol. Similarly, an amino acid solution was prepared at a concentration of 100 mmol. It was confirmed that the peptide inhibitor of the present invention was identified based on the biochemical optimization and / or phage display and screened to have excellent binding and / or inhibitory properties.

assembly

The peptides were assembled using standard symphony protocol. The peptide sequence was assembled as follows: The resin (250 mg, 0.14 mmol) in each reaction vial was washed with 4 ml of DMF twice and then quenched with 2.5 ml of 20% 4-methylpiperidine (Fmoc deprotection). The resin was then filtered, washed twice with DMF (4 ml) and again with N-methylpiperine for 30 min. The resin was washed again with DMF (4 ml) three times, then 2.5 ml of amino acid and 2.5 ml of HBTU-DIEA mixture were added. After frequent stirring for 45 min, the resin was filtered and washed three times with DMF (4 ml each time). Double couplings were performed on typical peptides of the invention. After completion of the coupling reaction, the mixture was washed three times with DMF (4 ml each time), and then the following amino acid coupling was carried out.

Closure of olefin-forming rings

The resin (100 μmol) was washed with 2 ml of DCM (3 × 1 min) followed by 2 ml of DCE (3 × 1 min), DCE (4.94 mg ml -1; ) Was treated with a solution consisting of 2 ml of 6 mM Grubbs' first-generation catalyst. The solution was refluxed overnight (12 h) under nitrogen and then drained. The resin was washed three times with DMF (4 ml each time), washed with DCM (4 ml), dried and cut.

cut

After completion of the peptide assembly, treatment with a cleavage reagent such as reagent K (82.5% trigrouoroacetic acid, 5% water, 5% thioanisole, 5% phenol, 2.5% 1,2-ethanedithiol) . The cleavage reagent was able to successfully cleave peptides from the resin as well as from all remaining side chain protecting groups.

The cleaved peptide was precipitated with cold diethyl ether and washed twice with ethyl ether. The filtrate was drained, a second aliquot of cold ether was added and the process was repeated. The crude peptide was dissolved in a solution of acetonitrile: water (7: 3 with 1% TFA) and filtered. Subsequently, the quality of the linear peptide was confirmed using ESI-MS (Micromass / Waters ZQ) and then purified.

Disulfide bond formation through oxidation

Peptides containing free thiols (e. G. DiPen) were assembled on the Link amide-MBHA resin according to the general Fmoc-SPPS method. The peptide was cleaved from the resin by treatment with a cleavage reagent (90% trifluoroacetic acid, 5% water, 2.5% 1,2-ethanedithiol, 2.5% tri-isopropylsilane). The cleaved peptide was precipitated with cold diethyl ether and washed twice with ethyl ether. The filtrate was drained, a second aliquot of cold ether was added and the process was repeated. The crude peptide was dissolved in a solution of acetonitrile: water (7: 3 with 1% TFA) and filtered to obtain the desired non-oxidized peptide peptide peptide.

X4 and X9 comprise Cys, Pen, hCys, (D) Pen, (D) Cys or (D) hCys were dissolved in 20 ml of water: acetonitrile. Saturated iodine in acetic acid was then added dropwise with stirring until yellow color persisted. The solution was stirred for 15 minutes and the reaction monitored by analytical HPLC and LCMS. When the reaction was complete, solid ascorbic acid was added until the solution became clear. First, water was diluted and then eluted with a reverse phase HPLC machine (Luna C18 support, 10 u, 100 A, mobile phase A: water containing 0.1% TFA, mobile phase B: acetonitrile (ACN) containing 0.1% , The gradient starting at 5% B and changing to 50% B over 60 minutes at a flow rate of 15 ml / min) to purify the solvent mixture. The fraction containing the pure product was then freeze-dried on a freeze-dryer.

Lactam bond formation

100 mg of crude, digested peptides (approximately 0.12 mmol) are dissolved in 100 ml of anhydrous dichloromethane. After addition of HOBt (1-hydroxybenzotriazole hydrate) (0.24 mmol, 2 equiv), DIEA (N, N-diisopropylethylamine) (1.2 mmol, 10 equiv) and TBTU (O- Yl) -N, N, N ', N'-tetramethyluronium tetrafluoroborate) (0.24 mmol, 2 eq.). The mixture is stirred overnight and then the reaction is carried out by HPLC. After completion of the reaction, the dichloromethane was evaporated, diluted with water and acetonitrile, and then purified by reversed phase HPLC machine (Luna C18 support, 10 u, 100 A, mobile phase A: water containing 0.1% TFA, mobile phase B: 0.1% TFA (Gradient, starting at 5% B and changing to 50% B over 60 minutes at a flow rate of 15 ml / min). The fraction containing the pure product is then lyophilized on a freeze-dryer.

Triazole bond formation

Purified peptides containing the relevant amino acid alkynes and azides at pH 7.4 were stirred in phosphate / MeOH (2: 1) at room temperature (1 mg per 2 ml). The addition of CuSO4 · 5 H ₂ O (10 eq), and sodium ascorbate (10 eq.) And the mixture was stirred for 36 h at room temperature. MeOH was removed and the solution was acidified to pH 3 using a 1% TFA water mix. The solution was then filtered and then loaded onto HPLC for peptide purification.

Thioether bond formation

Peptides containing free thiols (e. G., Cys) and hSer (OTBDMS) on link amide-MBHA resin were assembled according to the general Fmoc-SPPS method. The resin was treated with PPh ₃ (10 eq.) And Cl ₃ CCN (10 eq.) In DCM for 2 h to effect chlorination. The peptide was cleaved from the resin by treatment with a cleavage reagent (90% trifluoroacetic acid, 5% water, 2.5% 1,2-ethanedithiol, 2.5% tri-isopropylsilane). The cleaved peptide was precipitated with cold diethyl ether and washed twice with ethyl ether. The filtrate was drained, a second aliquot of cold ether was added and the process was repeated. The crude peptide was dissolved in a solution of acetonitrile: water (7: 3 with 1% TFA) and filtered to obtain the desired non-cyclized crude peptide.

Containing a free thiol (e.g., Cys, Pen, hCys, (D) Pen, (D) Cys or (D) hCys) and an alkyl halide (hSer (Cl)) at X4 and X9 positions or X9 and X4 positions Was dissolved in 0.1 M TRIS buffer (pH 8.5). Lt; / RTI &gt; overnight at RT. First, water was diluted 2-fold with water and then eluted with a reverse phase HPLC machine (Luna C18 support, 10 u, 100 A, mobile phase A: water containing 0.1% TFA, mobile phase B: acetonitrile (ACN) containing 0.1% Started at 5% B and changed to 50% B over 60 minutes at a flow rate of 15 ml / min) to purify the solvent mixture. The fraction containing the pure product was then freeze-dried on a freeze-dryer.

Selenoether bond formation

The crude peptide containing thiol protected-selenium amino acid and alkyl halide at positions X4 and X9 was dissolved in 0.1 M sodium phosphate buffer (pH 5.5) containing DTT (40 eq.). RT for 24 h. The solution was then diluted 2-fold with water and the final cyclized peptides were purified using RP-HPLC to give selenoethers.

Diselenide bond formation

The diselenide precursor was dissolved in a solution of 0.1 M phosphate buffer (pH 6.0) and isopropanol containing DTT (40 eq.) And the reaction mixture was incubated at 37 ° C. After 20 h elapsed, additional DTT (10 eq) was added to the reaction. After a total of 32 h elapsed, the cyclization reaction was diluted 2-fold with water and the final cyclized peptide was purified using RP-HPLC to give the decelanide.

refine

High performance liquid chromatography (HPLC) was performed on the Gemini C18 column (4.6 mm x 250 mm) (Phenomenex) for analytical reversed phase analysis. Semi-preparative reversed phase HPLC on a Gemini 10 urn C18 column (22 mm x 250 mm) (Penomenex) or Jupiter 10 urn, 300 A ° C18 column (21.2 mm x 250 mm) (Penomenex) Respectively. Using a linear gradient of B in Buffer A (mobile phase A: water containing 0.15% TFA, mobile phase B: acetonitrile (ACN) containing 0.1% TFA) min (separation). Using a linear gradient of B in Buffer A (mobile phase A: water containing 0.15% TFA, mobile phase B: acetonitrile (ACN) containing 0.1% TFA) min (separation).

Linker activation and dimerization

Peptide monomer subunits were linked as described below to form a peptide dimer inhibitor.

Small DIG Linker Activation Procedure : Add 5 mL of NMP to a glass vial containing IDA discrete (304.2 mg, 1 mmol), N-hydroxysuccinimide (NHS, 253.2 mg, 2.2 eq. 2.2 mmol) and stir bar Respectively. The mixture was stirred at room temperature to completely dissolve the solid starting material. N, N'-Dicyclohexylcarbodiimide (DCC, 453.9 mg, 2.2 eq., 2.2 mmol) was then added to the mixture. Precipitation was observed within 10 min and the reaction mixture was further stirred overnight at room temperature. The reaction mixture was then filtered to remove precipitated dicyclohexylurea (DCU). Prior to use for dimerization, the activated linkers were stored in sealed vials. The normal concentration of activated linker was approximately 0.20 M.

In the case of dimerization using a PEG linker, it does not include a preactivating step. A commercially available, preactivated bifunctional PEG linker was used.

Dimerization method : 2 mL of anhydrous DMF was added to the vial containing the peptide monomer (0.1 mmol). The pH of the peptide was adjusted to 8-9 using DIEA. The activated linker (IDA or PEG13, PEG 25) (0.48 eq, 0.048 mmol compared to monomer) was then added to the monomer solution. The reaction mixture was stirred at room temperature for 1 hour. The dimerization reaction completion was monitored using analytical HPLC. The completion time of the dimerization reaction varied depending on the linker. After completion of the reaction, the peptide was precipitated in cold ether and centrifuged. The supernatant ether layer was discarded. The precipitation step was repeated twice. The crude dimer was then subjected to reverse phase HPLC (Luna C18 support, 10 u, 100 A, mobile phase A: water containing 0.1% TFA, mobile phase B: acetonitrile (ACN) containing 0.1% TFA, gradient 15% B , Changing to 45% B over 60 minutes at a flow rate of 15 ml / min). The fraction containing the pure product was then freeze-dried on a freeze-dryer.

Example 2

Characterization of peptide inhibition of the binding of interleukin-23 to the interleukin-23 receptor

Peptide optimization was performed to identify peptide inhibitors of IL-23 signaling that were active at low concentrations (e.g., IC50 < 10 nM) while showing gastrointestinal (GI) stability. Specific peptides were tested to identify peptides that inhibit the binding of IL-23 to human IL-23R and inhibit IL-23 / IL-23R functional activity, as described below. The peptides tested include, for example, peptides comprising various cyclisation chemistries, including cyclic amides (side-chain cyclization), peptides including disulfide bonds between two Pen residues, and thioether linkages &Lt; / RTI &gt; Peptide inhibitors of the present invention include, but are not limited to, peptides having any of the structures shown herein. In addition, the peptide inhibitors of the present invention having the same amino acid sequence or a peptide structures described without the need to have at the same or any other N- or C- terminal "capping" groups, such as, Ac or NH ₂ branches, herein .

Assays performed to determine peptide activity are described below and the results of the assays are presented in Tables E3a-3h, E4a and E4b, E5a-E5c, E6, E7, and E8 below. The human ELISA represents the IL-23-IL-23R competitive binding assay described below, the rat ELISA represents the rat IL-23R competitive binding ELISA assay described below, and pStat3HTRF represents the DB cell IL-23R pSTAT3 cell assay . The peptides shown in Tables E3b-3e are cyclized through disulfide bridges formed between two cysteine residues in the peptide. The peptides shown in Table E3f are dimerized via the linker moiety as well as through the inner cysteine moiety. The peptides shown in Tables E4a and 4b are cyclized through two Pen residues present in each of these peptides. The peptides shown in Table E5a are those that are cyclized via thioether linkages between the indicated amino acid residues. Table E5b provides an exemplary structure showing thioether cyclization (which is indicated in the table by the term "cyclo ", with the cyclic region immediately followed by parentheses). The monomeric subunits of the peptide dimers shown in Table E5c are cyclized, as indicated by the term "cyclo ", and are linked to each other through the specified linker. The peptides shown in Table E6 are cyclized via ring closed metathesis of the indicated moiety. Table E7 provides two exemplary structures showing side cyclization via cyclic amide, in which the peptides are cyclized as indicated below the term "cyclo ". Table E8 shows the peptides that are cyclized through the cysteine residues and Pen residues.

The peptide inhibitors of the present invention include both a non-cyclized form, as well as a cyclized form of the peptide as set forth herein. For certain peptides, the residue Abu is present as specified, while in other embodiments related to the non-cyclized form, Abu may be referred to as hSer (Cl) or a homo-Ser residue.

IL-23- IL-23R Competitive Binding ELISA

Immulon (R) 4HBX plates were coated with 50 ng / well IL-23R_huFC and incubated overnight at 4 &lt; 0 &gt; C. Wells were washed 4 times with PBST, blocked with PBS containing 3% skim milk for 1 hour at room temperature, and washed again with PBST 4 times. A final concentration of 2 nM IL-23 diluted in a serial dilution of the test peptide and in a buffer for assay (PBS containing 1% skim milk) was added to each well and incubated at room temperature for 2 hours. The wells were washed and then incubated with 50 ng / well of goat anti-p40 polyclonal antibody (R &amp; D Systems # AF309) diluted in assay buffer for 1 hour at room temperature to bind bound IL-23 Respectively. The wells were washed again with PBST four times. Subsequently, a secondary antibody, HRP conjugated donkey anti-goat IgG (Jackson ImmunoResearch Laboratories # 705-035-147) diluted 1: 5,000 in the buffer for assay was added and incubated at room temperature And incubated for 30 minutes. Finally, the plate was washed as above. Signals were visualized using a TMB One Component HRP Membrane Substrate, quenched with 2 M sulfuric acid, and read at 450 nm by spectrometry. The IC50 values for the various test peptides measured from the data are given in Tables E3a-E3h, E4a and E4b, E5a-E5c, E6, E7, and E8.

Rat IL-23R Competitive Binding ELISA

The plate for assay was coated with 300 ng / well of rat IL-23R_huFC and incubated overnight at 4 ° C. The wells were washed, blocked, and washed again. Serial dilutions of the test peptide and IL-23 at a final concentration of 7 nM were added to each well and incubated at room temperature for 2 hours. After washing the wells, IL-23 bound with goat anti-p40 polyclonal antibody followed by HRP conjugated donkey anti-goat IgG was detected. The signal was visualized using a TMB one component HRP membrane substrate and quenched with 2 M sulfuric acid. The IC50 values for the various test peptides measured from the data are given in Tables E3g, E3h, E4a, E4b, E5b, E5c and E8.

DB cell IL-23R pSTAT3 cell assay

IL-23 plays a central role in supporting and maintaining Th17 differentiation in vivo. This process is believed to be mediated primarily through the signal transducer and activator of transcription 3 (STAT3), and is associated with RORC and pro-inflammatory activity through phosphorylation of STAT3 (via which pSTAT3 is obtained) ) IL-17 is upregulated. In this cell assay, pSTAT3 levels in IL-23R-expressing DB cells stimulated with IL-23 in the presence of the test compound were investigated. DB cells (ATCC # CRL-2289) cultured in RPMI-1640 medium (ATCC # 30-2001) supplemented with 10% FBS and 1% glutamine were seeded in 5x10E5 cells / well in 96 well tissue culture plates . Serial dilutions of the test peptides and IL-23 at a final concentration of 0.5 nM were added to each well and incubated at 37 [deg.] C for 30 minutes in a 5% CO ₂ humidified incubator. A change in phospho-STAT 3 level in the cell lysate was detected using a kit for assaying Cisbio HTRF pSTAT3 cells according to the manufacturer's two-plate assay protocol. The IC50 values measured from the data are presented as absolute values or values in the tables E3e, E3g, E3h, E4a, E4b, E5b, E5c and E8. If not, the data was not measured.

[Table E3a]

[Table E3b]

[Table E3c]

[Table E3d]

[Table E3e]

[Table E3f]

[Table E3g]

[Table E3h]

[Table E4a]

[Table E4b]

[Table E5a]

[Table E5b]

[Table E5c]

[Table E5d]

[Table E6]

[Table E7]

[Table E8]

SAR analysis of the activity of the tested peptide inhibitors revealed that CXXXXC disulfide was associated with high activity. Two Trp residues and Phe residues are also associated with high activity, but these amino acids have been recognized to be easily interchangeable with similar homologues (e.g., Trp is substituted by 1-Nal and / or Tyr is replaced by Phe). In addition, this data suggested that the presence of one or more basic residues at the C-terminus is associated with high activity. In addition, His-9 can be replaced by Arg or another homologue and can maintain or improve activity. The following schematic provides an exemplary consensus sequence showing specific residues associated with high activity.

Example 3

The stability of peptide inhibitors in artificial intestinal fluid ( SIF ), artificial gastric juice ( SGF ) and redox conditions

Studies were conducted on artificial intestinal fluid (SIF) and artificial gastric juice (SGF) to evaluate the gastric stability of the peptide inhibitors of the present invention. In addition, studies were conducted to evaluate the redox stability of the peptide inhibitors of the present invention.

6.8 g of monobasic potassium phosphate and 10.0 g of pancreatin were added to 1.0 L of water to prepare SIF. After dissolution, the pH was adjusted to 6.8 using NaOH. A DMSO stock (2 mM) for the test compound was first prepared. Aliquots of DMSO solution were each divided into six individual tubes, each containing 0.5 mL of SIF, preheated to 37 &lt; 0 &gt; C. The final test compound concentration was 20 μM. During the test, the vials were stored in a benchtop thermomixer (R). At each time point (0, 5, 10, 20, 40, 60, or 360 minutes or 24 hours), 1.0 mL of acetonitrile containing 1% formic acid was added to each vial to quench the reaction. Samples were stored at 4 &lt; 0 &gt; C until the end of the experiment. After sampling at the final time point, the tubes were mixed and centrifuged at 3,000 rpm for 10 minutes. Aliquots of supernatant were removed, diluted 1: 1 with distilled water containing internal standards and analyzed by LCMS / MS. The percentage of residue remaining at each time point was calculated based on the highest area ratio of the test compound to the internal standard. The time point 0 was set to 100%, and the values at all subsequent time points were calculated relative to the time point 0. The half life was calculated by fitting to the first order exponential decay equation using a graph pad. The stability in the SIF assay is shown in Tables E9 and E10 below.

SGF (final pH = 2) was prepared by adding 20 mg NaCl, 32 mg porcine pepsin (MP Biochemicals, catalog 02102599), and 70 ul HCl to 10 ml water. Aliquots of SGF (0.5 ml each) were prewarmed at 37 &lt; 0 &gt; C. To initiate the reaction, 1 [mu] l of peptide stock solution (10 mM in DMSO) was added to 0.5 ml SGF and mixed thoroughly to give a final peptide concentration of 20 [mu] M. The reaction was incubated at 37 [deg.] C with gentle shaking. At each time point (0, 15, 30, 60 min) an aliquot of 50 μl was removed and the reaction was terminated by addition to 200 μl acetonitrile containing 1% formic acid. Samples were stored at 4 &lt; 0 &gt; C until centrifugation and centrifuged at 10,000 rpm for 5 minutes. Aliquots of supernatant were removed, diluted 1: 1 with distilled water containing internal standards and analyzed by LCMS / MS. The percentage of residue remaining at each time point was calculated based on the highest area ratio of the test compound to the internal standard. The time point 0 was set to 100%, and the values at all subsequent time points were calculated relative to the time point 0. The half life was calculated by fitting to the first order exponential decay equation using a graph pad. The stability in the SGF assay is shown in Tables E9 and E10.

[Table E9]

[Table E10]

For each peptide tested, DTT stability assays were performed by adding 5 [mu] l of a 10 mM peptide stock solution in DMSO to 1 ml of 100 mM Tris-Cl (pH 7.5) (final peptide concentration was 50 [mu] M). At 0 min, 5 ul of freshly thawed 100 mM DTT solution was added to the incubation tube containing the peptides, resulting in a final DTT concentration of 0.5 mM. The reaction was incubated at room temperature. At different times up to 120 min (20 min, 40 min, 80 min, 120 min), aliquots of 50 μl were removed and 10 μl of 5 M acetic acid was added to terminate the reaction. To determine the disappearance of the parent peptide, samples (30 l) quenched by reversed-phase HPLC and UV absorbance at 220 nm were analyzed. The fraction of the oxidized residue was plotted against time and the half life was calculated by fitting to the first order exponential decay equation using Excel. The results of this study are presented in Table E11 below. All peptides with a half-life of > 120 min are considered stable.

[Table E11]

Example 4

Cross-reactivity of peptide inhibitors

The amino acids of the extracellular domain of human IL-23R are 95%, 77% and 70% identical to the cyno IL-23R, rat IL-23R and mouse IL-23R, respectively. Interestingly, mouse receptors contain insertions of 21 residues that are not present in human, mouse, chimpanzee, dog and cattle receptors. These additional amino acids are located in the region in which human IL-23R is considered to bind to IL-23.

The ability of certain peptide inhibitors capable of inhibiting human IL-23R, syn IL-23R, rat IL-23R and murine IL-23R to identify peptidic inhibitors cross-reacting with species other than human IL-23R ELISA assay. As shown by the observation of the sequence difference between human IL-23R and mouse IL-23R, the peptide antagonist tested showed no inhibitory activity or very weak inhibitory activity in mouse IL-23R ELISA (see Table E12). In contrast, to date, the tested antibodies showed similar efficacy on rat receptors and slightly less activity on synoceptors.

A variety of biological assays performed to measure the potency, cross-reactivity, and selectivity of IL-23R antagonists are described below.

Assay for selectivity of specific IL-23R antagonist

Human IL-12R? 1 ELISA

The plate for assay was coated with 100 ng / well of human IL-12R? 1_huFC and incubated overnight at 4 占 폚. The wells were washed, blocked, and washed again. Serial dilutions of the test peptide and IL-23 at a final concentration of 2.5 nM were added to each well and incubated at room temperature for 2 hours. After washing the wells, IL-23 bound with goat anti-p40 polyclonal antibody followed by HRP conjugated donkey anti-goat IgG was detected. The signal was visualized using a TMB one component HRP membrane substrate and quenched with 2 M sulfuric acid.

Mouse IL-23R Competitive Binding ELISA

The plate for assay was coated with 50 ng / well of mouse IL-23R_huFC and incubated overnight at 4 ° C. The wells were washed, blocked, and washed again. Serial dilutions of the test peptide and IL-23 at a final concentration of 4 nM were added to each well and incubated at room temperature for 2 hours. After washing the wells, IL-23 bound with goat anti-p40 polyclonal antibody followed by HRP conjugated donkey anti-goat IgG was detected. The signal was visualized using a TMB one component HRP membrane substrate and quenched with 2 M sulfuric acid.

Rat IL-23R Competitive Binding ELISA

The plate for assay was coated with 300 ng / well of rat IL-23R_huFC and incubated overnight at 4 ° C. The wells were washed, blocked, and washed again. Serial dilutions of the test peptide and IL-23 at a final concentration of 7 nM were added to each well and incubated at room temperature for 2 hours. After washing the wells, IL-23 bound with goat anti-p40 polyclonal antibody followed by HRP conjugated donkey anti-goat IgG was detected. The signal was visualized using a TMB one component HRP membrane substrate and quenched with 2 M sulfuric acid.

Syno IL-23R Competitive Binding ELISA

The plate for assay was coated with 50 ng / well of Sino IL-23R_huFC and incubated overnight at 4 ° C. The wells were washed, blocked, and washed again. Serial dilutions of the test peptide and IL-23 at a final concentration of 2 nM were added to each well and incubated at room temperature for 2 hours. After washing the wells, IL-23 bound with goat anti-p40 polyclonal antibody followed by HRP conjugated donkey anti-goat IgG was detected. The signal was visualized using a TMB one component HRP membrane substrate and quenched with 2 M sulfuric acid.

[Table E12]

Example 5

NK cell assay

Natural killer (NK) cells (Miltenyi Biotech, catalog number 130-092-657) purified from human peripheral blood of healthy donors by IL-2 (RnD, catalog number 130-092-657) at 25 ng / (RPMI 1640 containing 10% FBS, L-glutamine, and penicillin-streptomycin) in the presence of 10 &lt; 6 &gt; After 7 days, the cells were centrifuged and resuspended in complete medium with 1E6 cells / mL. Recombinant IL-23 and 10 ng / mL IL-18 (RnD, catalog number B003-5) of previously measured EC50 to EC75 were mixed with various concentrations of peptides and added to NH cells seeded with 1E5 cells per well . After 20 to 24 hours, Quantumine ELISA (RnD, Catalog No. DIF50) was used to quantify IFNγ in the supernatant.

[Table E13]

[Table 14]

Example 6

Characterization of biological inhibitors of peptide inhibitors

A variety of biological assays developed for this purpose, and described below, were used to measure the potency, cross-reactivity, and selectivity of certain peptide inhibitors.

Rat spleen cell assay

The new assay method developed was the rat splenocyte assay. This assay tested the level of IL-17A in activated rat splenocytes after stimulation with IL-23 in the presence of the test compound.

Briefly, freshly isolated spleen cells from rats were seeded in 96 well tissue culture plates in complete medium containing IL-1 [beta]. After distributing serial dilutions of test compound to each well with final concentration, i.e., rat IL-23 between EC50 and EC80 values; Plates were incubated for 3 days at 37 [deg.] C in a 5% CO ₂ humidified incubator. ELISA was used to detect changes in IL-17A levels in the supernatant.

Rat colitis model: 3 days DSS-containing drinking water for 9 days

There is a set of evidence in the literature that demonstrates the pathogenic role of IL-23 / IL-23R signaling in animal models of colitis. In the case of IL-23 ligands, the above requirements may be applicable to IL-10 ^{- / -} spontaneous colitis model, Helicobacter hepaticus- induced colitis model, anti-CD40 congenital colitis model, and chronic CD45RB ^high CD4 ⁺ T cell delivery model. In the case of the IL-23 receptor, the requirement for colitis was found in the chronic CD45RB ^and CD4 ⁺ T cell delivery models as well as acute colitis models induced by DSS or by anti-CD40. Certain peptide inhibitors of the present invention did not cross-react with the IL-23 receptor from mice, but from rats it was recognized that a rat model with IBD associated with the IL-23 pathway was developed.

In this model, colonic illness was induced in SD rats by unlimited exposure to drinking water containing 3% DSS until day 9. Disease Activity Index (DSS) between three study groups (n = 6 rats / group) with 3% DSS using vehicle, 3% DSS, and positive control (receiving PO at 100 mg / kg of sulfasalazine as QD) (DAI) score and colon weight: the ratio of colon length was compared. The DAI score consisted of three parameters, including weight loss (%), stiffness, and quantitative occlusion score, and was able to achieve a maximum of 3 units. Animals exposed to DSS continued to have significantly elevated DAI scores from day 4 (as compared to vehicle control) and DAI peaked at approximately 2.5 at the end of the study (day 9). When the rats exposed to DSS were treated with a positive control (sulfasalazine), the disease score (compared to DSS alone) decreased from day 5. Colonic weight observed at the late stage for animals with sulfasalazine treatment and untreated DSS induced disease: the difference in the ratio of the length of the colon was also significant.

In vitro activity and stability

Two peptides (compounds A and B) were selected for use in the further biological studies presented below. And the other one contained a Pen-Pen disulfide bond. The activity, selectivity and in vitro stability profile of the two compounds are provided herein.

Assays for the selectivity of peptide inhibitors included measurement of production of IL-12 in human IL-12Rb1 ELISA and PHA-activated human PBMC, which is briefly described below.

Human IL-12R? 1 ELISA

The plate for assay was coated with 100 ng / well of human IL-12Rb1_huFC and incubated overnight at 4 ° C. The wells were washed, blocked, and washed again. Serial dilutions of the test peptide and IL-23 at a final concentration of 2.5 nM were added to each well and incubated at room temperature for 2 hours. After washing the wells, IL-23 bound with goat anti-p40 polyclonal antibody followed by HRP conjugated donkey anti-goat IgG was detected. The signal was visualized using a TMB one component HRP membrane substrate and quenched with 2 M sulfuric acid. The data obtained from this assay is provided herein.

Production of IFNy by IL-12 in PHA-activated human PBMC

This assay examined the ability of IL-23R antagonists to neutralize the production of IFNγ protein in human PBMC stimulated by IL-12. IL-23R peptide inhibitors specific to the IL-23 / IL-23R pathway are not expected to alter IFN gamma production levels. In this assay, Compounds A and B were tested and a graph showing that the compound did not alter IFN gamma production levels at most of the concentrations tested is shown in FIG.

In vivo activity

Acute colitis was induced by feeding 3% (wt / vol) DSS dissolved in drinking water to female Sprague Dawley. Starting on the same day as DSS, compound A or B was orally administered at 20 mg / kg or 30 mg / kg three times a day for 9 days. Compound A was also administered intraperitoneally three times daily at 30 mg / kg. The neutralizing anti-IL-23p19 antibody was used as a comparative group and was administered intraperitoneally at 4 mg / kg on the same day and 5 days after DSS start. To quantify the clinical activity of colitis, three parameters were measured: weight (scale 0-3), stool (scale 0-3), and occlusive blood (scale 0-3), as shown in Table E15 below. The mean disease activity index (DAI) was measured daily for each animal as an average. Upon autopsy, the entire colon from the cecum to the rectum was removed. Colon length was measured, flushed with PBS to remove feces, weighed, opened to length and visually scored. Visual impairment of the colon was scored as scale 0-3, as shown in Table E16 below.

Table E17 below shows that Compound A and B treatment significantly improved DAI scores on Day 7 when compared to the vehicle group. Figure 1 shows the results for DAI values from day 7. In addition, there was a significant reduction in the ratio of colon-colony length to colon-macroscopic score (FIG. 3). The reduction in inflammation observed in the case of orally delivered peptides was similar to that observed from neutralizing anti-IL-23p19 monoclonal antibodies. Statistical analysis of significance was compared to vehicle-treated groups and measured using a Student's T-test (graph pad prism). Differences were recognized significantly. * p <0.05, ** p <0.01, *** p <0.001, **** p <0.0001.

[Table E15]

[Table E16]

[Table E17]

Example 7

In vitro assay and surface plasmon resonance (SPR) analysis

An in vitro assay and SPR were performed to further characterize the following compound, the following compound C:

By performing the assays described in the previous examples, Compound C inhibited IL-23-dependent upregulation of phosphor-STAT 3 (pSTAT3) and strong inhibition of IFN gamma production in human peripheral blood mononuclear cells (PB NK) Lt; RTI ID = 0.0 &gt; IL-23R &lt; / RTI &gt; In addition, Compound C showed little inhibition on human IL6R or in the IL-12-dependent production of IFNy on PBMC in cell-free ELISA and was selective. The data are presented in Table E18a below. Compound C also cross-reacted with cynomolgus IL-23R (IC50 7 nM) and rat IL-23R (IC50 17 nM) and inhibited IL-23-dependent IL-17A production in rat splenocytes (IC50 130 nM ) (Data not shown).

[Table E18a]

After oral administration to rats at a PO dose of 20 mg / kg, exposure of compound C was also limited to GI, and the AUC value was 355 ug.h / g for the small intestine mucosa; 77 ug.h / g for colon mucosa; In the case of plasma, it was 0.3 ug.h / mL and the recovery rate in stool was 40%.

Compound C also has a SIF half-life > 24 h; SGF half life> 24 h; The human sarcosis half-life was> 24 h, and the half-life in the DTT assay was> 2 h, which was stable in various GI solutions and reducing environments.

SPR experiments were performed using a Biacore CM4 and a Biacore 2000 device equipped with a Xantec HC1500m sensor chip and a T100 optical biosensor. A mixture of recombinant human IL-23R_huFC (RnD), or recombinant human IL-12Rβ1_huFC (RnD) or two receptor subunits was captured on the anti-human IgG surface. Recombinant human IL-23 (Humanzyme) or Compound C was used as the analyte. The SPR sensorgram was fitted to a 1: 1 interaction model to roughly estimate the association rate constant (k _on ), dissociation rate constant (k _off ) and dissociation constant (K _D ) of the complex as shown in Table E11 below . The data show that Compound C binds to the mixed surface of IL-23R, and IL-12R? 1 and IL-23R with similar potencies of 2.42 nM and 2.56 nM, respectively, without binding to IL-12R? The affinity for IL-23R is similar to that from IL-23. In contrast, the affinity of IL-23 to the mixed surface is approximately 14x faster than from compound C.

[Table E18b]

Example 8

The efficacy of IL-23R antagonists in TNBS induced colitis in rats

To further assess the efficacy of IL-23R antagonists in animal models of disease, 2,4,6-trinitrobenzenesulfonic acid (TNBS) (TNBS / ethanol) in 45% -50% 60 mg / kg to 7 week old female Sprague Dawley to induce acute colitis. Compound C (as described in Example 7) was orally administered at 20 mg / kg or 6.7 mg / kg three times per day, and approximately 24 hours before TNBS inoculation (day -1) 0.0 &gt; mg / mL &lt; / RTI &gt; or 0.2 mg / mL, respectively. Neutralizing anti-IL-23p19 antibody was used as a comparative group and was administered intraperitoneally at 4 mg / kg on day -1 and on day 3 again. All animals received orally received a PBS (pH 7.4) vehicle used to formulate Compound C. The study design is shown in FIG.

To assess the degree of inflammation, animals were observed daily for clinical signs, including weight loss (%), and for dilute stool or diarrhea symptoms. Six days after TNBS inoculation, the rats were sacrificed and the total colon length from the cecum to the rectum from each animal and the colon weight was recorded. Colitis severity was assessed by a pathologist blinded to treatment identity. In addition to the colon wall thickness, visually colon lesions were scored based on 0-4 scales according to Table E19 and histopathological scores were determined based on the following parameters (Tables E20 and E21 below).

[Table E19]

[Table E20]

[Table E21]

When compared to the mock group, rats tested with TNBS experienced acute weight loss, increased incidence of dilated stool, and increased ratio of length to weight of colon. The data were verified by visual inspection of the colon with slight colonic damage characterized by erythema, edema and small erosion. Compound C treatment attenuated this change when compared to the TNBS colitis group. High doses of Compound C reduce the ratio of the colon weight to length by r, reduce the thickness of the colon wall, and, more importantly, significantly improve the visual pathological score of the colon in 70% . At low doses, statistical significance was observed in all of the above indications, except for the thickness of the colon wall, although the trend was evident. The reduction in inflammation observed when orally delivered Compound C was similar to that observed from neutralizing anti-IL-23p19 monoclonal antibodies (Figure 6).

Histological examination of the H & E stained distal colon revealed that most of the lesions observed from the vehicle group were characterized by necrosis with inflammatory cells across the entire thickness of the colon, the presence of necrotic tissue debris on the luminal surface, As shown in Fig. Animals treated with compound C showed localized lesions localized to the mucosa and submucosa, and colon tissues showed potential signs of healing at necrotic areas. Specifically, animals treated with 160 mg / kg / d compound C showed a significant reduction of inflammation, mucosal necrosis and colon wall thickness when compared to that of anti-IL-23p19 antibody control, (Fig. 7).

Concentration analysis of the samples collected 1 hour after the final PO dosing showed that the plasma concentration of Compound C detected from all animals was ≤2X less than the IC75 measured in the rat splenocyte / IL-17A cell-based assay or rat IL-23R ELISA , Suggesting that the efficacy observed from the oral treatment is most likely due to its local activity in the colon (Figure 8). Taken together, the data highlight the protective effect of IL-23R antagonists in the development of TNBS colitis.

This study demonstrates that the peptides of the present invention are potent, selective, orally potent IL-23R peptide antagonists, which are promising therapeutic agents for the treatment of IBD and other disorders. As provided herein, the invention is a potent blocker of IL-23 / IL-23R signaling in human cell lines and human primary cells; Is selective for L-23R, does not inhibit binding to IL-6R or signaling through IL-12R; Rats and cynomolgus, as well as mouse homologs, thereby enabling in vivo studies on said species; Resistant to the proteolytic and reducing environment of GI and thus offers the advantage of being potentially safe as compared to a systemically delivered drug by showing a high drug level in the intestinal tissue and a limited drug concentration in the circulation; Most significantly provide peptides that are effective in attenuating colitis in a TNBS-induced rat colitis model through activity such as GI-restricted activity and which are analogous to anti-IL-23p19 monoclonal antibodies.

Example  9

Exemplary IL-23R antagonists In vitro  Characterization

In order to evaluate the properties of the efficacy of IL-23R peptide antagonists of SEQ ID NO: 980 (peptide 980), 993 (peptide 993), and 1185 (peptide 1185), experiments for measuring the efficacy, Was performed as described. The IL-23 / IL-23R competitive binding assay (performed as described above in Example 2) for human (Hu), Cynomolgus monkey (Cyno), and Rat IL-23 and IL- the IC ₅₀ values of peptides measured in a quantitative ELISA for are shown in Table E22. In addition, the efficacy of the peptides was assessed by the IL-23R activity assay as described above. Reduction in the levels of phospho-STAT3 (pSTAT3) (human DB cell (pSTAT3) performed in Example 2 above) in human DB cells exposed to IL-23; Reduction of IFN gamma (Hu NK cells; performed as described in Example 5 above) produced with human NK cells exposed to IL-23; And IC ₅₀ values of the peptides were determined as determined by reduction of IL-17A (rat (spleen), performed as described in Example 6 above) produced with activated splenocytes exposed to IL-34. Selectivity was assessed by measuring IC ₅₀ values of peptides that inhibited human IL-23 / IL-12R beta 1 interactions (see Example 4) or human IL-6 / IL-6R interactions (see Example 6) . Peptide stability was assessed by measuring the half-life of peptides exposed to artificial intestinal fluid (SIF), artificial gastric juice (SGF), or human intestinal fluid (SIF).

[Table E22]

The structure of peptide 993 is shown below:

[2-Nal] - [4-amino-4-carboxy-tetrahydrobenzo [b] thiophene- pyran] -ENN-NH ₂ (SEQ ID NO: 993)

The structure of peptide 1185 is shown below:

Ac- [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] )] - NN-NH ₂ (SEQ ID NO: 1185)

The structure of peptide 980 is shown below:

- [2-Nal] - [4-amino-4-carboxy-tetrahydropyran] -ENN-NH- [Phe [4- (2-aminoethoxy) ₂ (SEQ ID NO: 980)

The results are summarized in Table E22 and show that the peptides strongly and selectively inhibit IL-23 / IL-23R binding compared to IL-23 / IL-12R beta1 or IL-6 / IL-6R interactions. This inhibition was confirmed by cell culture assays measuring IL-23R-dependence, such as STAT3 phosphorylation, IFN gamma production, and IL-17A production. In addition, peptides were measured to have high stability when exposed to artificial intestinal fluid, artificial gastric juice, or human intestinal fluid.

Data from human DB cell (pSTAT3) experiments were used for shield analysis (see FIG. 17). For shield analysis, concentrations of 0.3 nM, 1 nM, 3 nM, 10 nM, 30 nM and 100 nM of peptide 993 were tested. The shield slope was determined to be 1.068, which means that peptide 993 acts as a simple competitive antagonist. In addition, a shield analysis was performed on a peptide having the structure of SEQ ID NO: 1169, which has a structure very similar to that of peptide 1185. The shield slope was determined to be 0.91, which means that peptides with similar structures, including peptide 1185, are likely to act as simple competitive antagonists. In addition, a shield analysis was performed on the peptide of SEQ ID NO: 1211 having a structure similar to that of peptide 980. The shield slope was determined to be 0.76. However, when the slope was fixed at 1, the R ² value was 0.975. This data suggests that peptides with similar structures, including peptide 1185, may act as simple competitive antagonists.

Example  10

Exemplary IL-23R antagonists In vivo  drug Dynamics

The pharmacokinetic properties of the exemplary peptides were determined in vivo. Sprague Dawley rats were given peptide 993 at 10 mg / kg P.O.

A single oral dose of peptide 933 was administered to normal female Sprague Dawley rats (N = 3 rats per point) with or without drinking water provided with unlimited drinking water (see FIG. 11). After oral administration, exposure of peptide 993 was measured in plasma at 0.25, 0.5, 1, 3, 6, 8, and 24 hours after administration. Also, the level of peptide 993 was measured in the small intestine, colon, small intestine, colon mucosa, intestinal mucus, peyer's patch and intestinal membrane lymph nodes (MLN) at 1, 3, 6, 8 and 24 hours after administration . Urine and feces were collected at 6 and 24 hours to determine the excretion of peptide 993. Plasma, feces and tissue samples were stored at -80 ± 10 ° C prior to analysis. For plasma, compounds were extracted by protein precipitation using a 50 μL sample and a quench solution with internal standards (MeOH: ACN w / 0.1% formic acid, 50:50 volume). For faeces, the samples were homogenized with 0.1% formic acid in water (4: 1 water: feces ratio) prior to extraction. The compound was extracted by protein precipitation using a final solution (MeOH: ACN w / 0.1% formic acid, 50:50 volume) with internal standard, using 50 μL of the fecal homogenate. For tissues such as the colon or small intestine, the samples were homogenized with 0.1% formic acid (3: 1 water: tissue ratio) in water prior to extraction. For tissues such as phagocytic and intestinal membrane lymph nodes, samples were homogenized with 0.1% formic acid (20: 1 water: tissue ratio) in water prior to extraction. The compound was extracted by protein precipitation using a final solution (MeOH: ACN w / 0.1% formic acid, 50:50 volume) with internal standard, using 50 μL of the tissue homogenate. The precipitated protein was removed with a filter plate, and the collected supernatant was dried and reconstituted. The treated samples were analyzed on an AB / MDS Sciex API 4000 mass spectrometer. Positive ions were monitored in a multiple reaction-monitoring (MRM) mode. Peak area ratio.

No detectable level of peptide 993 was observed in rat plasma between 0 and 24 hours after administration (see FIG. 11A). Conversely, there was a detectable level of peptide 993 for at least 6 hours in the phage plate and small intestine after administration (see FIGS. 11B and 11C) and in the colon for at least 8 hours after administration (FIG. Peptides 993 at levels greater than 5% of the total dose administered in rat faeces at 24 hours after administration were detected, further indicating that peptide 993 has a high degree of oral stability. Taken together, these results demonstrate that peptide 993 is an orally stable GI-restricted peptide with high GI content and limited systemic distribution following oral administration.

Sprague Dawley rats were given peptide 1185 at 10 mg / kg P.O. A single oral dose of peptide 1185 was administered to normal female Sprague Dawley rats (N = 3 per view). After oral administration, exposure of peptide 1185 was measured in plasma of samples taken up to 8 hours after dosing. Urine and feces were collected for several hours to determine the excretion of peptide 1185 (FIG. 18).

Sprague Dawley rats were administered peptide 980 at 10 mg / kg P.O. A single oral dose of peptide 980 was administered to normal female Sprague Dawley rats (N = 3 per view). After oral administration, exposure of the peptide 980 was measured in the plasma of samples taken up to 8 hours after administration. Urine and feces were collected for several hours to determine the excretion of peptide 980 (Fig. 19).

Example  11

The stability profile of an exemplary IL-23R antagonist

The stability profile of an exemplary peptide inhibitor has been characterized. Peptide 993 and peptide 1185 were evaluated in a stability panel that tested binding to 44 panels of the panel. The target included a G protein coupled receptor (GPCR), a transporter such as a dopamine transporter (DAT) and an ion channel. For all targets, these peptides did not exhibit activity, as defined by a change in activity (inhibition or stimulation) of the target by more than 25%. Targets tested in the stability panel are listed in Table E24. For each target, peptide 993 and peptide 1185 were determined to be inactive at a concentration of up to 10 μM. The stability profile of peptide 980 was evaluated by testing the compound selected from Table E24. For all compounds tested, peptide 980 showed only mild activity (33%) in the acetylcholinesterase assay, unless otherwise indicated any activity as defined by a change in the activity of the target in excess of 25% Respectively.

[Table E24]

Example  12

Acute colitis Rat  Effect of Exemplary Peptide Inhibitors in the Model

To evaluate the efficacy of peptide 1185, an exemplary peptide inhibitor in animal disease models, acute colitis was induced by administration of 64 mg / kg TNBS in 50% ethanol to female Sprague Dawley rats at 7 days old at day 0. Peptide 1185 was orally administered at 37 mg / kg / day (combined PO and drinking water), PO BID, -1 to 7 days. A sham group not exposed to TNBS and a TNBS treated group treated with vehicle were used as a control. For comparison, the neutralized anti-IL-23p19 antibody was intraperitoneally administered at 4 mg / kg on day -1 and again on day 3, and prednisolone was administered 10.0 mg / day to P.O. . All animals were orally provided with water, such as vehicle used to formulate peptide 993.

As described above, animals were observed daily for clinical signs, including weight loss and dilute stool or diarrhea. Six days after TNBS inoculation, the rats were sacrificed and the total colon length and colon weight for each animal was recorded. The severity of colitis was assessed by pathologists. In addition to the colon wall thickness, total colon damage scores were measured for 0-5 scales according to Table E29 below and histopathological scores were determined based on the parameters described in Table E30.

Treatment with peptide 1185 significantly reduced some disease parameters observed in the TNBS rat model of acute colitis. Rats in the simulated group continued to gain weight during the study, whereas rats exposed to TNBS and vehicle treated rats suffered weight loss. Oral treatment with prednisolone or whole body treatment with anti-IL-23p19 prevented weight loss in TNBS-exposed rats. Treatment with orally administered peptide 1185 did not significantly prevent weight loss in the TNBS test infected rats (see FIG. 13). In addition, a significant reduction in the ratio of colon weight to length was observed after treatment with prednisolone or anti-IL-23p19, as compared to vehicle treatment. Oral administration of peptide 1185 showed a similar decrease in colon weight to colon length ratio and colon visibility score in TNBS exposed rats. Higher colon visual scores mean higher degrees of colon pathology. Colonoscopic scores were determined by scoring for adhesion, stenosis, ulceration, and colon wall thickness, all of which were significantly increased by treatment with prednisolone, anti-IL-23p19, or peptide 1185 compared to the vehicle- Respectively. These data demonstrate that oral administration of peptide 1185 has an efficacy comparable to systemic administration of anti-IL-23p19 monoclonal antibody.

The pathological characterization of tissue sections from the colon taken from rats in the simulated group, vehicle, anti-IL-34p19 and peptide 1185 groups was investigated. Mucosal inflammation, transmural inflammation, line loss and erosion were scored according to the criteria described in Table E29. For all of these specificities, treatment with anti-IL-23p19 or prednisolone reduced the histopathological scores associated with TNBS exposure. Treatment with peptide 1185 did not significantly reduce histopathological scores.

Example  13

Acute colitis Rat  Effect of Exemplary Peptide Inhibitors in the Model

To evaluate the efficacy of peptide 993, an exemplary IL-23R peptide inhibitor in animal disease models, acute colitis was induced by administration of 64 mg / kg TNBS in 50% ethanol to female Sprague Dawley rats at 7 days old at day 0. Peptide 993 was orally administered for 8 days starting at (D-1) at about 24 hours before TNBS inoculation at 10 mg / kg twice daily, 42 mg / kg / day total. The TNBS treated groups treated with the simulated group and the vehicle not exposed to TNBS were used as a control group. All animals were orally challenged with the vehicle used to formulate peptide 993.

As described above, animals were observed daily for clinical signs, including weight loss and dilute stool or diarrhea. Six days after TNBS inoculation, the rats were sacrificed and the total colon length and colon weight for each animal was recorded. The severity of colitis was assessed by pathologists. In addition to the colon wall thickness, total colon damage scores were measured for 0-5 scales according to Table E29 below and histopathological scores were determined based on the parameters described in Table E30.

Treatment with peptide 993 significantly reduced all disease parameters observed in the TNBS rat model of acute colitis. Rats in the simulated group continued to gain weight during the study, whereas rats exposed to TNBS and vehicle treated rats suffered weight loss. In addition, oral treatment with peptide 993 prevented weight loss in rats infested with TNBS test (see FIG. 12). In addition, after oral administration of peptide 993, a significant decrease in the ratio of the weight to the length of the colon was observed. Higher colon visual scores mean a higher degree of colon pathology, which was significantly reduced by treatment with peptide 993 as compared to the vehicle treated control. Oral administration of peptide 993 has an efficacy comparable to systemic administration of anti-IL-23p19 monoclonal antibody acting as a positive control. Histopathologic scores were significantly reduced in the colon from the peptide 993 treated rats as compared to the vehicle group.

Example  14

Acute colitis Rat  Effect of Exemplary Peptide Inhibitors in the Model

To evaluate the efficacy of peptide 980, an exemplary IL-23R peptide inhibitor in animal disease models, acute colitis was induced by administration of 64 mg / kg TNBS in 50% ethanol to female Sprague Dawley rats at 7 days old at day 0. Peptide 980 was orally administered at 37 mg / kg / day (combined PO and drinking water), PO BID, -1 to 7 days. The TNBS treated groups treated with the simulated group and the vehicle not exposed to TNBS were used as a control group. All animals were orally challenged with the vehicle used to formulate peptide 980.

As described above, animals were observed daily for clinical signs, including weight loss and dilute stool or diarrhea. Six days after TNBS inoculation, the rats were sacrificed and the total colon length and colon weight for each animal was recorded. The severity of colitis was assessed by pathologists. In addition to the colon wall thickness, the total crystalline damage score was measured for 0-5 scales according to Table E29 below and the histopathological score was determined based on the parameters described in Table E30. Treatment with peptide 980 significantly reduced all disease parameters observed in the TNBC rat model of acute colitis.

Treatment with orally administered peptide 980 prevented weight loss in TNBS test-infected rats (see FIG. 14). In addition, after oral administration of peptide 980, a significant decrease in the ratio of the weight of the colon to the length of the colon was observed. Higher colon visual scores indicate a higher degree of colon pathology, which was significantly reduced by treatment with peptide 980 as compared to the vehicle treated control (see FIG. 14).

The pathological characterization of tissue sections from the colon collected from rats in the simulated group, vehicle and peptide 980 group was investigated. Mucosal inflammation, inflammation through the wall, line loss and erosion (see Figure 14d) were scored according to the criteria set forth in Table E30. The sum of histopathological scores was significantly reduced by peptide 980 treatment compared to vehicle.

Example  15

Acute colitis Rat  After treatment with the peptide inhibitor in the model Biomarker  level

The levels of inflammatory markers in the colon were examined. Specimens of the designated colon tissues were collected and rapidly frozen for protein expression analysis. For protein extraction, the samples were thawed, weighed and homogenized in extraction buffer (PBS pH 7.2 supplemented with protease inhibitor, 3x volume: weight). The homogenate was centrifuged at 13 krpm for 15 minutes at 4 ° C for a total of 2 times to remove the debris. The supernatant was stored at -80 캜 in aliquots and then it was used for protein expression analysis on ELISA. Total protein in each sample was quantified using the BCA assay. Expression of MPO, IL-l [beta], IL-6, IL-17A and IL-22 in the distal colon samples was analyzed using commercially available rat ELISA kits.

Treatment with peptide 993 reduced the level of inflammatory markers present in the colon. The disease definitions (MPO, IL-6 and IL-1 beta) and IL-23 directed biomarkers (IL-22 and IL-17A) were reduced by treatment with peptide 993 as compared to vehicle- 15). These data demonstrate that administration of an amount of peptide 993, which can reduce in vivo pathology, also reduces the level of biomarkers present in the colon associated with IL-23R activity. Treatment with peptide 980 reduced MPO and IL-22 levels compared to vehicle-treated controls (see FIG. 16). Treatment of the tested dose of peptide 1185 did not significantly reduce the levels of MPO, IL-22, or IL-17A.

[Table E29]

[Table E30a]

[Table E30b]

[Table E30c]

 [Table E30d]

[Table E30e]

[Table E30f]

Example  16

Interkine -23 Interkine Characterization of Additional Peptide Suppression for Binding to the -23 Receptor

Peptide optimization was performed to identify additional peptide inhibitors of IL-23 signaling that are active at low concentrations (e.g., IC50 < 10 nM) or that exhibit gastrointestinal (GI) stability. Certain peptides were tested to identify peptides that inhibit the binding of IL-23 to human IL-23R and inhibit IL-23 / IL-23R functional activity as described below. The peptides tested include peptides containing a variety of different cyclisation chemistries including, for example, peptides containing disulfide bonds between the two Pen residues, and peptides incorporating thioether linkages. Peptide inhibitors of the present invention include, but are not limited to, peptides having any structure shown herein. In addition, the peptide inhibitors of this invention, including the same or have the same amino acid sequence of a peptide or structure described herein, which is any N- or C- terminal "capping" groups, for example, Ac or NH _2, or do not have them do.

Assays performed to determine peptide activity were performed as described in Example 2 above. The human ELISA means the IL23-IL23R competitive binding assay, the rat ELISA means the rat IL-23R competitive binding assay, and the pStat3HTRF means the DB cell IL-23R pSTAT3 cell assay. The peptides shown in Table E31 are cyclized via disulfide bonds formed between two residues in these peptides. The peptides shown in Table E32 are cyclized via thioether linkages between the indicated amino acid residues. Table E32 provides an exemplary structure depicting the thioether cyclization, which may appear in the table as the term "cyclo ", and has a ring region immediately followed by parentheses.

[Table E31]

[Table E32]

The IC50 of an exemplary peptide inhibitor (thioether)

Example  17

Artificial intestinal fluid ( SIF ), Artificial gastric juice SGF ) And the stability of additional peptide inhibitors under redox conditions

Studies were conducted in artificial intestinal fluid (SIF) and artificial gastric juice (SGF) to assess the gastric stability of additional peptide inhibitors of the present invention. In addition, studies were conducted to evaluate the redox stability of additional peptide inhibitors of the present invention.

[Table E33]

Example  18

NK  Cell assay method

Natural killer (NK) cells (Miltenyi Biotech, Cat # 130-092-657) purified from human peripheral blood of healthy donors by IL-2 (RnD, Cat # 202-IL-010 / CF) in complete medium (RPMI 1640 containing 10% FBS, L-glutamine and penicillin-streptomycin). After 7 days, the cells were centrifuged and resuspended in complete medium with 1E6 cells / mL. Recombinant IL-23 and 10 ng / mL IL-18 (RnD, Cat # B003-5) of previously measured EC50 to EC75 were mixed with various concentrations of peptides and added to NK cells seeded with 1E5 cells per well . After 20 to 24 hours, Quantumine ELISA (RnD, Cat # DIF50) was used to quantify IFN gamma in the supernatant. Various results are shown in Table E34. The various results shown for a single peptide are from a separate assay.

[Table E34]

The US patents, US patent application publications, US patent applications, foreign patents, foreign patent applications, and non-patent publications referred to herein and / or listed in the application datasheet are incorporated herein by reference in their entirety.

Although specific embodiments of the invention have been described herein for purposes of illustration, it will be understood from the foregoing that various changes may be made without departing from the spirit and scope of the invention. Accordingly, the invention is not limited except as by the appended claims.

                               SEQUENCE LISTING <110> PROTAGONIST THERAPEUTICS, INC.   <120> PEPTIDE INHIBITORS OF INTERLEUKIN-23 RECEPTOR AND THEIR USE TO TREAT INFLAMMATORY DISEASES <130> IPA171447-US &Lt; 150 > PCT / US15 / 40658 <151> 2015-07-15 <150> US 14 / 800,627 <151> 2015-07-15 &Lt; 150 > US 62 / 264,820 <151> 2015-12-08 &Lt; 150 > US 62 / 281,123 <151> 2016-01-20 <160> 1114 <170> PatentIn version 3.5 <210> 1 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Aib <220> <221> MOD_RES <222> (2) (2) <223> Aib <220> <221> MOD_RES &Lt; 222 > (11) <223> Aib <400> 1 Xaa Xaa Thr Trp Gln Asp Tyr Trp Leu Tyr Xaa Arg 1 5 10 <210> 2 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 2 Cys Ala Met Thr Trp Gln Asp Tyr Trp Leu Tyr Gly Arg Cys 1 5 10 <210> 3 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Aib <220> <221> MOD_RES <222> (2) (2) <223> Aib <400> 3 Xaa Xaa Thr Trp Gln Asp Tyr Trp Leu Tyr Gly Arg 1 5 10 <210> 4 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 4 Ala Met Thr Trp Gln Asp Tyr Trp Leu Tyr Gly Arg Lys 1 5 10 <210> 5 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 5 Cys Ala Met Thr Trp Gln Asp Tyr Trp Leu Tyr Gly Arg Cys Lys 1 5 10 15 <210> 6 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 6 Lys Ala Met Thr Trp Gln Asp Tyr Trp Leu Tyr Gly Arg 1 5 10 <210> 7 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 7 Lys Cys Ala Met Thr Trp Gln Asp Tyr Trp Leu Tyr Gly Arg Cys 1 5 10 15 <210> 8 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (5) <223> Aib <400> 8 Ala Met Thr Trp Xaa Asp Tyr Trp Leu Tyr Gly Arg 1 5 10 <210> 9 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 9 Ala Met Thr Trp Gln Asp Tyr Trp Leu Tyr Gly Arg 1 5 10 <210> 10 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 10 Ala Met Thr Trp Gln Asp Tyr Trp Leu Tyr Gly Arg 1 5 10 <210> 11 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 11 Ala Ala Thr Trp Gln Asp Tyr Trp Leu Tyr Gly Arg 1 5 10 <210> 12 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 12 Ala Met Ala Trp Gln Asp Tyr Trp Leu Tyr Gly Arg 1 5 10 <210> 13 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 13 Ala Met Thr Ala Gln Asp Tyr Trp Leu Tyr Gly Arg 1 5 10 <210> 14 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 14 Ala Met Thr Trp Ala Asp Tyr Trp Leu Tyr Gly Arg 1 5 10 <210> 15 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 15 Ala Met Thr Trp Gln Ala Tyr Trp Leu Tyr Gly Arg 1 5 10 <210> 16 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (10) <223> Cha <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 16 Cys Gln Asp Trp Gln Cys Tyr Trp Arg Xaa Phe Gly Xaa Lys 1 5 10 <210> 17 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (10) <223> Octgly <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 17 Cys Gln Thr Trp Gln Cys Tyr Trp Arg Gly Phe Gly Xaa Lys 1 5 10 <210> 18 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (10) <223> Dap <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 18 Cys Gln Thr Trp Gln Cys Tyr Trp Lys Xaa Phe Gly Xaa Lys 1 5 10 <210> 19 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (10) <223> Dap <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 19 Cys Gln Thr Trp Gln Cys Tyr Trp His Xaa Phe Gly Xaa Lys 1 5 10 <210> 20 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 20 Cys Gln Thr Trp Gln Cys Tyr Trp Arg Leu Phe Gly Xaa Lys 1 5 10 <210> 21 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hArg <220> <221> MOD_RES &Lt; 222 > (10) <223> Dap <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 21 Cys Gln Thr Trp Gln Cys Tyr Trp Arg Xaa Phe Gly Xaa Lys 1 5 10 <210> 22 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> Cit <220> <221> MOD_RES &Lt; 222 > (10) <223> Dap <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 22 Cys Gln Thr Trp Gln Cys Tyr Trp Xaa Xaa Phe Gly Xaa Lys 1 5 10 <210> 23 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 23 Cys Gln Thr Trp Gln Cys Tyr Trp Arg Val Phe Gly Xaa Lys 1 5 10 <210> 24 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (10) <223> Dap <220> <221> MOD_RES &Lt; 222 > (11) <223> Tic <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 24 Cys Gln Thr Trp Gln Cys Tyr Trp Arg Xaa Xaa Gly Xaa Lys 1 5 10 <210> 25 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (8) <223> Tic <220> <221> MOD_RES &Lt; 222 > (9) <223> Orn <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 25 Cys Gln Thr Trp Gln Cys Tyr Xaa Xaa Lys Phe Gly Xaa Lys 1 5 10 <210> 26 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (10) <223> Dab <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 26 Cys Gln Thr Trp Gln Cys Tyr Trp Arg Xaa Phe Gly Xaa Lys 1 5 10 <210> 27 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> Orn <220> <221> MOD_RES &Lt; 222 > (10) <223> Dap <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 27 Cys Gln Thr Trp Gln Cys Tyr Trp Xaa Xaa Phe Gly Xaa Lys 1 5 10 <210> 28 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 28 Cys Gln Thr Trp Gln Cys Tyr Trp His Glu Asn Gly Ala Lys 1 5 10 <210> 29 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 29 Cys Arg Thr Trp Gln Cys Tyr Trp Arg Glu Asn Gly Ala Lys 1 5 10 <210> 30 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 30 Cys Arg Thr Trp Gln Cys Tyr Trp Arg Glu Tyr Gly Ala Lys 1 5 10 <210> 31 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (2) (2) <223> N-MeAla <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 31 Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Xaa Lys 1 5 10 <210> 32 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (13) <223> Beta-Ala <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 32 Cys Ala Asp Trp Val Cys Tyr Trp Arg Lys Phe Gly Ala Lys 1 5 10 <210> 33 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> Cit <220> <221> MOD_RES &Lt; 222 > (13) <223> Beta-Ala <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 33 Cys Ala Asp Trp Val Cys Tyr Trp Xaa Lys Phe Gly Ala Lys 1 5 10 <210> 34 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> Cit <220> <221> MOD_RES &Lt; 222 > (10) <223> Tle <220> <221> MOD_RES &Lt; 222 > (13) <223> Beta-Ala <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 34 Cys Ala Asp Trp Val Cys Tyr Trp Xaa Xaa Phe Gly Ala Lys 1 5 10 <210> 35 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> Cit <220> <221> MOD_RES &Lt; 222 > (10) <223> t-butyl-Ala <220> <221> MOD_RES &Lt; 222 > (13) <223> Beta-Ala <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 35 Cys Ala Asp Trp Val Cys Tyr Trp Xaa Ala Phe Gly Ala Lys 1 5 10 <210> 36 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> Cit <220> <221> MOD_RES &Lt; 222 > (10) <223> Cha <220> <221> MOD_RES &Lt; 222 > (13) <223> Beta-Ala <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 36 Cys Ala Asp Trp Val Cys Tyr Trp Xaa Xaa Phe Gly Ala Lys 1 5 10 <210> 37 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (8) <223> 1-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Cit <220> <221> MOD_RES &Lt; 222 > (13) <223> Beta-Ala <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 37 Cys Ala Asp Trp Val Cys Tyr Xaa Xaa Val Phe Gly Ala Lys 1 5 10 <210> 38 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> Cit <220> <221> MOD_RES &Lt; 222 > (13) <223> Beta-Ala <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 38 Cys Ala Asp Trp Val Cys Tyr Trp Xaa Val Phe Gly Ala Lys 1 5 10 <210> 39 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> Cit <220> <221> MOD_RES &Lt; 222 > (10) <223> Chg <220> <221> MOD_RES &Lt; 222 > (13) <223> Beta-Ala <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 39 Cys Ala Asp Trp Val Cys Tyr Trp Xaa Xaa Phe Gly Ala Lys 1 5 10 <210> 40 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> Cit <220> <221> MOD_RES &Lt; 222 > (10) <223> Beta-Ala <220> <221> MOD_RES &Lt; 222 > (13) <223> Beta-Ala <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 40 Cys Ala Asp Trp Val Cys Tyr Trp Xaa Ala Phe Gly Ala Lys 1 5 10 <210> 41 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> Tle <220> <221> MOD_RES &Lt; 222 > (10) <223> Tle <220> <221> MOD_RES &Lt; 222 > (13) <223> Beta-Ala <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 41 Cys Ala Asp Trp Val Cys Tyr Trp Xaa Xaa Phe Gly Ala Lys 1 5 10 <210> 42 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> Tle <220> <221> MOD_RES &Lt; 222 > (13) <223> Beta-Ala <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 42 Cys Ala Asp Trp Val Cys Tyr Trp Xaa Lys Phe Gly Ala Lys 1 5 10 <210> 43 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> D-Ala <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 43 Cys Gln Thr Trp Gln Cys Tyr Trp Ala Val Phe Gly Xaa Lys 1 5 10 <210> 44 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> Beta-Ala <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 44 Cys Gln Thr Trp Gln Cys Tyr Trp Ala Val Phe Gly Xaa Lys 1 5 10 <210> 45 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> D-Leu <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 45 Cys Gln Thr Trp Gln Cys Tyr Trp Leu Val Phe Gly Xaa Lys 1 5 10 <210> 46 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> D-Phe <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid   <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys   <400> 46 Cys Gln Thr Trp Gln Cys Tyr Trp Phe Val Phe Gly Xaa Lys 1 5 10 <210> 47 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> D-Asn <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid   <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys   <400> 47 Cys Gln Thr Trp Gln Cys Tyr Trp Asn Val Phe Gly Xaa Lys 1 5 10 <210> 48 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> D-Thr <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid   <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys   <400> 48 Cys Gln Thr Trp Gln Cys Tyr Trp Thr Val Phe Gly Xaa Lys 1 5 10 <210> 49 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> D-Asp <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid   <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys   <400> 49 Cys Gln Thr Trp Gln Cys Tyr Trp Asp Val Phe Gly Xaa Lys 1 5 10 <210> 50 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> Cit <220> <221> MOD_RES &Lt; 222 > (10) <223> D-Leu <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 50 Cys Gln Thr Trp Gln Cys Tyr Trp Xaa Leu Phe Gly Xaa Lys 1 5 10 <210> 51 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> Cit <220> <221> MOD_RES &Lt; 222 > (10) <223> D-Phe <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 51 Cys Gln Thr Trp Gln Cys Tyr Trp Xaa Phe Phe Gly Xaa Lys 1 5 10 <210> 52 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> Cit <220> <221> MOD_RES &Lt; 222 > (10) <223> D-Asn <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 52 Cys Gln Thr Trp Gln Cys Tyr Trp Xaa Asn Phe Gly Xaa Lys 1 5 10 <210> 53 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> Cit <220> <221> MOD_RES &Lt; 222 > (10) <223> D-Thr <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 53 Cys Gln Thr Trp Gln Cys Tyr Trp Xaa Thr Phe Gly Xaa Lys 1 5 10 <210> 54 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> Agp <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 54 Cys Gln Thr Trp Gln Cys Tyr Trp Xaa Val Asn Gly Xaa Lys 1 5 10 <210> 55 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (8) <223> alpha-MeTrp <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 55 Cys Gln Thr Trp Gln Cys Tyr Trp Arg Val Asn Gly Xaa Lys 1 5 10 <210> 56 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (8) <223> alpha-MeTrp <220> <221> MOD_RES &Lt; 222 > (9) <223> Cit <220> <221> MOD_RES &Lt; 222 > (10) <223> hLeu <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 56 Cys Gln Thr Trp Gln Cys Tyr Trp Xaa Leu Asn Gly Xaa Lys 1 5 10 <210> 57 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> Cit <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 57 Cys Gln Thr Trp Gln Cys Tyr Trp Xaa Val Asn Gly Xaa Lys 1 5 10 <210> 58 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> Agp <220> <221> MOD_RES &Lt; 222 > (10) <223> Dap <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 58 Cys Gln Thr Trp Gln Cys Tyr Trp Xaa Xaa Asn Gly Xaa Lys 1 5 10 <210> 59 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> Cit <220> <221> MOD_RES (12). (12) <223> D-Ala <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 59 Cys Gln Thr Trp Gln Cys Tyr Trp Xaa Val Phe Ala Xaa Lys 1 5 10 <210> 60 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> Cit <220> <221> MOD_RES (12). (12) <223> D-Leu <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 60 Cys Gln Thr Trp Gln Cys Tyr Trp Xaa Val Phe Leu Xaa Lys 1 5 10 <210> 61 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> Cit <220> <221> MOD_RES (12). (12) <223> D-Phe <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 61 Cys Gln Thr Trp Gln Cys Tyr Trp Xaa Val Phe Phe Xaa Lys 1 5 10 <210> 62 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> Cit <220> <221> MOD_RES (12). (12) <223> D-Asn <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 62 Cys Gln Thr Trp Gln Cys Tyr Trp Xaa Val Phe Asn Xaa Lys 1 5 10 <210> 63 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> Cit <220> <221> MOD_RES (12). (12) <223> D-Thr <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 63 Cys Gln Thr Trp Gln Cys Tyr Trp Xaa Val Phe Thr Xaa Lys 1 5 10 <210> 64 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> Cit <220> <221> MOD_RES (12). (12) <223> D-Asp <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 64 Cys Gln Thr Trp Gln Cys Tyr Trp Xaa Val Phe Asp Xaa Lys 1 5 10 <210> 65 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (2) (2) <223> N-MeArg <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 65 Cys Arg Thr Trp Gln Cys Tyr Trp Arg Val Phe Gly Xaa Lys 1 5 10 <210> 66 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (2) (2) <223> N-MeGln <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 66 Cys Gln Thr Trp Gln Cys Tyr Trp Arg Val Phe Gly Xaa Lys 1 5 10 <210> 67 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (2) (2) <223> Cit <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 67 Cys Xaa Thr Trp Gln Cys Tyr Trp Arg Val Phe Gly Xaa Lys 1 5 10 <210> 68 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> Orn <220> <221> MOD_RES &Lt; 222 > (10) <223> Dap <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 68 Cys Ala Asp Trp Val Cys Tyr Trp Xaa Xaa Phe Gly Xaa Lys 1 5 10 <210> 69 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (8) <223> 1-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Orn <220> <221> MOD_RES &Lt; 222 > (10) <223> Dap <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 69 Cys Ala Asp Trp Val Cys Tyr Xaa Xaa Xaa Phe Gly Xaa Lys 1 5 10 <210> 70 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (8) <223> D-Trp <220> <221> MOD_RES &Lt; 222 > (9) <223> Orn <220> <221> MOD_RES &Lt; 222 > (10) <223> Dap <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 70 Cys Ala Asp Trp Val Cys Tyr Trp Xaa Xaa Phe Gly Xaa Lys 1 5 10 <210> 71 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (8) <223> hPhe <220> <221> MOD_RES &Lt; 222 > (9) <223> Orn <220> <221> MOD_RES &Lt; 222 > (10) <223> Dap <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 71 Cys Ala Asp Trp Val Cys Tyr Phe Xaa Xaa Phe Gly Xaa Lys 1 5 10 <210> 72 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (8) <223> Beep <220> <221> MOD_RES &Lt; 222 > (9) <223> Orn <220> <221> MOD_RES &Lt; 222 > (10) <223> Dap <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 72 Cys Ala Asp Trp Val Cys Tyr Xaa Xaa Xaa Phe Gly Xaa Lys 1 5 10 <210> 73 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe (3,5-F2) <220> <221> MOD_RES &Lt; 222 > (9) <223> Orn <220> <221> MOD_RES &Lt; 222 > (10) <223> Dap <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 73 Cys Ala Asp Trp Val Cys Tyr Phe Xaa Xaa Phe Gly Xaa Lys 1 5 10 <210> 74 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe (CONH2) <220> <221> MOD_RES &Lt; 222 > (9) <223> Orn <220> <221> MOD_RES &Lt; 222 > (10) <223> Dap <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 74 Cys Ala Asp Trp Val Cys Tyr Phe Xaa Xaa Phe Gly Xaa Lys 1 5 10 <210> 75 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe (4-CF3) <220> <221> MOD_RES &Lt; 222 > (9) <223> Orn <220> <221> MOD_RES &Lt; 222 > (10) <223> Dap <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 75 Cys Ala Asp Trp Val Cys Tyr Phe Xaa Xaa Phe Gly Xaa Lys 1 5 10 <210> 76 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe (2,4-Me2) <220> <221> MOD_RES &Lt; 222 > (9) <223> Orn <220> <221> MOD_RES &Lt; 222 > (10) <223> Dap <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 76 Cys Ala Asp Trp Val Cys Tyr Phe Xaa Xaa Phe Gly Xaa Lys 1 5 10 <210> 77 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 77 Cys Met Thr Trp Gln Cys Tyr Trp Leu Tyr Gly Arg Xaa Lys 1 5 10 <210> 78 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (8) <223> Beta-hTrp <220> <221> MOD_RES &Lt; 222 > (9) <223> Orn <220> <221> MOD_RES &Lt; 222 > (10) <223> Dap <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 78 Cys Ala Asp Trp Val Cys Tyr Trp Xaa Xaa Phe Gly Xaa Lys 1 5 10 <210> 79 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> Orn <220> <221> MOD_RES &Lt; 222 > (10) <223> alpha-MeLeu <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 79 Cys Ala Asp Trp Val Cys Tyr Trp Xaa Leu Phe Gly Xaa Lys 1 5 10 <210> 80 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> Orn <220> <221> MOD_RES &Lt; 222 > (10) <223> Beta-spiral-pip <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 80 Cys Ala Asp Trp Val Cys Tyr Trp Xaa Xaa Phe Gly Xaa Lys 1 5 10 <210> 81 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (8) <223> 4-Phenylcyclohexylalanine <220> <221> MOD_RES &Lt; 222 > (9) <223> Orn <220> <221> MOD_RES &Lt; 222 > (10) <223> Dap <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 81 Cys Ala Asp Trp Val Cys Tyr Xaa Xaa Xaa Phe Gly Xaa Lys 1 5 10 <210> 82 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> Orn <220> <221> MOD_RES &Lt; 222 > (10) <223> Aib <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 82 Cys Ala Asp Trp Val Cys Tyr Trp Xaa Xaa Phe Gly Xaa Lys 1 5 10 <210> 83 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> Orn <220> <221> MOD_RES &Lt; 222 > (10) <223> Diethyl-Gly <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 83 Cys Ala Asp Trp Val Cys Tyr Trp Xaa Gly Phe Gly Xaa Lys 1 5 10 <210> 84 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (8) &Lt; 223 > Beta-MePhe (4-F) <220> <221> MOD_RES &Lt; 222 > (9) <223> Orn <220> <221> MOD_RES &Lt; 222 > (10) <223> Dap <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 84 Cys Ala Asp Trp Val Cys Tyr Phe Xaa Xaa Phe Gly Xaa Lys 1 5 10 <210> 85 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (8) <223> Beta-hPhe <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 85 Cys Gln Thr Trp Gln Cys Tyr Phe Arg Val Asn Gly Xaa Lys 1 5 10 <210> 86 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (8) <223> Beta-1-Nal <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 86 Cys Gln Thr Trp Gln Cys Tyr Xaa Arg Val Asn Gly Xaa Lys 1 5 10 <210> 87 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 87 Cys Ser Asp Trp Glu Cys Tyr Trp His Ile Phe Gly 1 5 10 <210> 88 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 88 Cys Glu Thr Trp Glu Cys Tyr Trp His Ser Phe Ser 1 5 10 <210> 89 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 89 Cys Gln Ser Trp Glu Cys Tyr Trp His Tyr Tyr Gly 1 5 10 <210> 90 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 90 Cys Ser Asp Trp Arg Cys Tyr Trp His Val Phe Gly 1 5 10 <210> 91 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 91 Cys His Thr Trp Val Cys Tyr Trp His Glu Phe Ser 1 5 10 <210> 92 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 92 Cys Thr Asp Trp Val Cys Tyr Trp His Glu Tyr Ser 1 5 10 <210> 93 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 93 Cys Gln Thr Trp Val Cys Tyr Trp His Thr Tyr Gly 1 5 10 <210> 94 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 94 Cys Gly Asn Trp Glu Cys Tyr Trp His Val Tyr Gly 1 5 10 <210> 95 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 95 Cys Lys Asp Trp Lys Cys Tyr Trp His Ile Tyr Gly 1 5 10 <210> 96 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 96 Cys Arg Thr Trp Val Cys Tyr Trp His Val Phe Gly 1 5 10 <210> 97 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (4) (4) <223> 1-Nal <400> 97 Cys Ala Asp Xaa Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 98 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (4) (4) <223> 2-Nal <400> 98 Cys Ala Asp Xaa Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 99 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (4) (4) <223> 1-Beep <400> 99 Cys Ala Asp Xaa Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 100 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (4) (4) <223> Tic <400> 100 Cys Ala Asp Xaa Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 101 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (4) (4) <223> Beta-hTrp <400> 101 Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 102 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (8) <223> 1-Beep <400> 102 Cys Ala Asp Trp Val Cys Tyr Xaa His Thr Phe Gly 1 5 10 <210> 103 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (8) <223> Tic <400> 103 Cys Ala Asp Trp Val Cys Tyr Xaa His Thr Phe Gly 1 5 10 <210> 104 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (8) <223> Beta-hTrp <400> 104 Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 105 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 105 Cys Ala Asp Trp Val Cys Tyr Ala His Thr Phe Gly 1 5 10 <210> 106 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 106 Ala Cys Asp Trp Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 107 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 107 Ala Cys Asp Trp Cys Cys Tyr Trp Cys Thr Phe Gly 1 5 10 <210> 108 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 108 Ala Ala Asp Trp Cys Ala Tyr Trp Cys Thr Phe Gly 1 5 10 <210> 109 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 109 Cys Ala Asp Trp Cys Cys Tyr Trp Cys Thr Phe Gly 1 5 10 <210> 110 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 110 Cys Ala Asp Trp Cys Cys Tyr Trp Cys Thr Phe Gly 1 5 10 <210> 111 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 111 Cys Ala Asp Trp Cys Cys Tyr Trp Cys Thr Phe Gly 1 5 10 <210> 112 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 112 Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe 1 5 10 <210> 113 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 113 Cys Ala Asp Trp Val Cys Tyr Trp His Thr 1 5 10 <210> 114 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 114 Cys Ala Asp Trp Val Cys Tyr Trp 1 5 <210> 115 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Beta-Ala <400> 115 Ala Ser Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 116 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> D-Lys <400> 116 Lys Ser Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 117 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> D-Lys <220> <221> MOD_RES <222> (2) (2) <223> Beta-Ala <400> 117 Lys Ala Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 118 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) (2-aminoethoxy) acetic acid <400> 118 Xaa Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 119 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> D-Lys <400> 119 Lys Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 120 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 120 Cys Lys Asp Trp Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 121 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 121 Cys Ala Asp Trp Lys Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 122 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 122 Cys Ala Asp Trp Val Cys Tyr Trp Lys Thr Phe Gly 1 5 10 <210> 123 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 123 Cys Ala Asp Trp Val Cys Tyr Trp His Lys Phe Gly 1 5 10 <210> 124 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 124 Cys Ala Asp Trp Val Cys Tyr Trp His Thr Lys Gly 1 5 10 <210> 125 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES (12). (12) <223> D-Lys <400> 125 Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Lys 1 5 10 <210> 126 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 126 Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 127 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (8) <223> 1-Nal <400> 127 Cys Ala Asp Trp Val Cys Tyr Xaa His Thr Phe 1 5 10 <210> 128 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (8) <223> 1-Nal <220> <221> MOD_RES &Lt; 222 > (11) N-Me-Phe <400> 128 Cys Ala Asp Trp Val Cys Tyr Xaa His Thr Phe 1 5 10 <210> 129 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (8) <223> 1-Nal <220> <221> MOD_RES &Lt; 222 > (10) <223> Sarc <400> 129 Cys Ala Asp Trp Val Cys Tyr Xaa His Xaa Phe 1 5 10 <210> 130 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (8) <223> 1-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> N-Me-His <400> 130 Cys Ala Asp Trp Val Cys Tyr Xaa His Thr Phe 1 5 10 <210> 131 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 131 Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Lys 1 5 10 <210> 132 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (2) (2) <223> Sarc <220> <221> MOD_RES &Lt; 222 > (8) <223> 1-Nal <400> 132 Cys Xaa Asp Trp Val Cys Tyr Xaa His Thr Phe 1 5 10 <210> 133 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (4) (4) <223> N-Me-Trp <220> <221> MOD_RES &Lt; 222 > (8) <223> 1-Nal <400> 133 Cys Ala Asp Trp Val Cys Tyr Xaa His Thr Phe 1 5 10 <210> 134 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (5) <223> Sarc <220> <221> MOD_RES &Lt; 222 > (8) <223> 1-Nal <400> 134 Cys Ala Asp Trp Xaa Cys Tyr Xaa His Thr Phe 1 5 10 <210> 135 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (8) <223> 1-Nal <220> <221> MOD_RES &Lt; 222 > (11) <223> D-Phe <400> 135 Cys Ala Asp Trp Val Cys Tyr Xaa His Thr Phe 1 5 10 <210> 136 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (8) <223> 1-Nal <220> <221> MOD_RES (12). (12) <223> Sarc <400> 136 Cys Ala Asp Trp Val Cys Tyr Xaa His Thr Phe Xaa 1 5 10 <210> 137 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 137 Cys Ala Thr Trp Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 138 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 138 Cys Ala Asp Trp Glu Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 139 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 139 Cys Ala Asp Trp Val Cys Tyr Trp His Arg Cys Gly Trp Trp Gly Cys 1 5 10 15 <210> 140 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (8) <223> 1-Nal <220> <221> MOD_RES &Lt; 222 > (10) <223> D-Ala <400> 140 Cys Ala Asp Trp Val Cys Tyr Xaa His Ala Phe Gly 1 5 10 <210> 141 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (8) <223> 1-Nal <220> <221> MOD_RES &Lt; 222 > (10) <223> Aib <400> 141 Cys Ala Asp Trp Val Cys Tyr Xaa His Xaa Phe Gly 1 5 10 <210> 142 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (8) <223> 1-Nal <220> <221> MOD_RES &Lt; 222 > (10) <223> beta-Ala <400> 142 Cys Ala Asp Trp Val Cys Tyr Xaa His Ala Phe Gly 1 5 10 <210> 143 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (8) <223> 1-Nal <400> 143 Cys Ala Asp Trp Val Cys Tyr Xaa Phe Thr Phe Gly 1 5 10 <210> 144 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (8) <223> 1-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> D-Ala <400> 144 Cys Ala Asp Trp Val Cys Tyr Xaa Ala Thr Phe Gly 1 5 10 <210> 145 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (8) <223> 1-Nal <220> <221> MOD_RES &Lt; 222 > (10) <223> Aib <220> <221> MOD_RES &Lt; 222 > (11) <223> D-Phe <400> 145 Cys Ala Asp Trp Val Cys Tyr Xaa His Xaa Phe Gly 1 5 10 <210> 146 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (8) <223> 1-Nal <220> <221> MOD_RES (12). (12) <223> Aib <400> 146 Cys Ala Asp Trp Val Cys Tyr Xaa His Thr Phe Xaa 1 5 10 <210> 147 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (8) <223> 1-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> N-Me-His <220> <221> MOD_RES &Lt; 222 > (10) <223> D-Ala <220> <221> MOD_RES (12). (12) <223> Aib <400> 147 Cys Ala Asp Trp Val Cys Tyr Xaa His Ala Phe Xaa 1 5 10 <210> 148 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (8) <223> 1-Nal <220> <221> MOD_RES &Lt; 222 > (10) <223> AEP <400> 148 Cys Ala Asp Trp Val Cys Tyr Xaa His Xaa Gly 1 5 10 <210> 149 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> N-MeHis <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 149 Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Xaa Lys 1 5 10 <210> 150 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (8) <223> Aic <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 150 Cys Ala Asp Trp Val Cys Tyr Xaa His Thr Phe Gly Xaa Lys 1 5 10 <210> 151 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (8) <223> Beep <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 151 Cys Ala Asp Trp Val Cys Tyr Xaa His Thr Phe Gly Xaa Lys 1 5 10 <210> 152 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> N-MeArg <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 152 Cys Gln Thr Trp Gln Cys Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 153 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (10) <223> N-MeArg <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 153 Cys Gln Thr Trp Gln Cys Tyr Trp Arg Arg Asn Gly Xaa Lys 1 5 10 <210> 154 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (10) <223> N-MeLys <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 154 Cys Gln Thr Trp Gln Cys Tyr Trp Arg Lys Asn Gly Xaa Lys 1 5 10 <210> 155 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (10) <223> Sarc <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 155 Cys Gln Thr Trp Gln Cys Tyr Trp Arg Xaa Asn Gly Xaa Lys 1 5 10 <210> 156 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (10) <223> D-Glu <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 156 Cys Gln Thr Trp Gln Cys Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 157 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> D-Arg <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 157 Cys Gln Thr Trp Gln Cys Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 158 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> D-Arg <220> <221> MOD_RES &Lt; 222 > (10) <223> D-Glu <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 158 Cys Gln Thr Trp Gln Cys Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 159 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> N-MeGlu <220> <221> MOD_RES (12). (12) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (13) <223> D-Lys <400> 159 Cys Gln Thr Trp Gln Cys Tyr Trp Glu Asn Gly Xaa Lys 1 5 10 <210> 160 <211> 6 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 160 Cys Ala Asp Trp Val Cys 1 5 <210> 161 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> N-MeArg <220> <221> MOD_RES &Lt; 222 > (13) <223> AEP <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 161 Cys Arg Asp Trp Gln Cys Tyr Trp Arg Lys Phe Gly Xaa Lys 1 5 10 <210> 162 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (10) <223> D-Lys <220> <221> MOD_RES &Lt; 222 > (13) <223> AEP <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 162 Cys Arg Asp Trp Gln Cys Tyr Trp Arg Lys Phe Gly Xaa Lys 1 5 10 <210> 163 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> D-Arg <220> <221> MOD_RES &Lt; 222 > (13) <223> AEP <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 163 Cys Arg Asp Trp Gln Cys Tyr Trp Arg Lys Phe Gly Xaa Lys 1 5 10 <210> 164 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> D-Arg <220> <221> MOD_RES &Lt; 222 > (10) <223> D-Lys <220> <221> MOD_RES &Lt; 222 > (13) <223> AEP <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 164 Cys Arg Asp Trp Gln Cys Tyr Trp Arg Lys Phe Gly Xaa Lys 1 5 10 <210> 165 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> N-MeArg <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 165 Cys Gln Thr Trp Gln Cys Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 166 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 166 Cys Thr Asp Trp Lys Cys Tyr Trp His Glu Phe Gly 1 5 10 <210> 167 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 167 Cys Arg Thr Trp Thr Cys Tyr Trp His Val Tyr Gly 1 5 10 <210> 168 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 168 Cys Pro Asn Trp Glu Cys Tyr Trp His Arg Phe Gly 1 5 10 <210> 169 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 169 Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 170 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 170 Cys Ala Asp Trp Met Cys Tyr Trp His Glu Tyr Gly 1 5 10 <210> 171 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 171 Cys Thr Thr Trp Lys Cys Tyr Trp His Gln Tyr Gly 1 5 10 <210> 172 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 172 Cys Ser Asn Trp Glu Cys Tyr Trp His His Tyr Gly 1 5 10 <210> 173 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 173 Cys Ser Asp Trp Val Cys Tyr Trp His Val Tyr Gly 1 5 10 <210> 174 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 174 Cys Asp Thr Trp Lys Cys Tyr Trp His Arg Gln Ser 1 5 10 <210> 175 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (8) <223> 1-Nal <400> 175 Cys Ala Asp Trp Val Cys Tyr Xaa His Thr Phe Gly 1 5 10 <210> 176 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <400> 176 Cys Ala Asp Trp Val Cys Tyr Xaa His Thr Phe Gly 1 5 10 <210> 177 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 177 Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 178 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (13) <223> D-Lys <400> 178 Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Lys 1 5 10 <210> 179 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (15) <223> D-Lys <400> 179 Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Ala Pro Lys 1 5 10 15 <210> 180 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 180 Cys Thr Asp Trp Lys Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 181 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 181 Cys Arg Asp Trp Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 182 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 182 Cys Ala Asp Trp Val Cys Tyr Trp His Glu Phe Gly 1 5 10 <210> 183 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 183 Cys Ala Asp Trp Val Cys Tyr Trp His Phe His Gln Leu Arg Asp Ala 1 5 10 15 <210> 184 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 184 Cys Ala Asp Trp Val Cys Tyr Trp His Glu His Ser Glu Arg Val Gly 1 5 10 15 <210> 185 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 185 Cys Ala Asp Trp Val Cys Tyr Trp His Asn His Ser Glu Gly Ser Gly 1 5 10 15 <210> 186 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 186 Cys Ala Asp Trp Val Cys Tyr Trp His Arg Ser Thr Gly Gly GInt His 1 5 10 15 <210> 187 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> D-Lys <220> <221> MOD_RES &Lt; 222 > (9) <223> 1-Nal <220> <221> MOD_RES &Lt; 222 > (13) <223> Sarc <220> <221> MOD_RES &Lt; 222 > (14) <223> AEP <220> <221> MOD_RES &Lt; 222 > (15) <223> D-Arg <400> 187 Lys Cys Arg Asp Trp Gln Cys Tyr Xaa His Thr His Xaa Xaa Arg 1 5 10 15 <210> 188 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 188 Thr Gln Phe Asp Cys Arg Thr Trp Glu Cys Tyr Trp His Thr Phe Gly 1 5 10 15 <210> 189 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 189 Gly Gly Val Glu Cys Asn Asp Trp Gln Cys Tyr Trp His Thr Phe Gly 1 5 10 15 <210> 190 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 190 Arg Glu Gly Thr Cys Ser Thr Trp Lys Cys Tyr Trp His Thr Phe Gly 1 5 10 15 <210> 191 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 191 Asp Thr Pro Arg Cys Arg Thr Trp Glu Cys Tyr Trp His Thr Phe Gly 1 5 10 15 <210> 192 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 192 Gly Gly Gly Glu Cys Glu Asn Trp Glu Cys Tyr Trp His Thr Phe Gly 1 5 10 15 <210> 193 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 193 Gly Asp His Lys Cys Ser Ser Trp Glu Cys Tyr Trp His Thr Phe Gly 1 5 10 15 <210> 194 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 194 Gly Ser Val His Cys Met Thr Trp Glu Cys Tyr Trp His Thr Phe Gly 1 5 10 15 <210> 195 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (8) <223> 1-Nal <400> 195 Cys Ala Asp Trp Val Cys Tyr Xaa Val Thr Phe Gly 1 5 10 <210> 196 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> D-His <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 196 Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Xaa Lys 1 5 10 <210> 197 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 197 Cys Arg Asp Trp Gln Cys Tyr Trp His Lys Phe Gly 1 5 10 <210> 198 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 198 Cys Ser Asn Trp Val Cys Tyr Trp His Thr Tyr Gly 1 5 10 <210> 199 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (13) <223> Beta-Ala <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 199 Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Ala Lys 1 5 10 <210> 200 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 200 Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Xaa Lys 1 5 10 <210> 201 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 201 Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 202 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (13) <223> AEP <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Arg <400> 202 Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Xaa Arg 1 5 10 <210> 203 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (13) <223> AEP <400> 203 Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Xaa Lys 1 5 10 <210> 204 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (13) <223> Gaba <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 204 Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Xaa Lys 1 5 10 <210> 205 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (13) <223> Hexanoic-D-Lys <400> 205 Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Lys 1 5 10 <210> 206 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (13) (PEG) 2-D-Lys <400> 206 Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Lys 1 5 10 <210> 207 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 207 Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Pro Lys 1 5 10 <210> 208 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (13) <223> Azt <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 208 Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Xaa Lys 1 5 10 <210> 209 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 209 Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Ala Lys 1 5 10 <210> 210 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (15) <223> D-Lys <400> 210 Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Ala Pro Lys 1 5 10 15 <210> 211 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (14) <223> Azt <220> <221> MOD_RES &Lt; 222 > (15) <223> D-Lys <400> 211 Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Ala Xaa Lys 1 5 10 15 <210> 212 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (15) <223> D-Lys <400> 212 Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Ala Ala Lys 1 5 10 15 <210> 213 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (13) <223> AEP <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 213 Cys Arg Asp Trp Gln Cys Tyr Trp His Lys Phe Gly Xaa Lys 1 5 10 <210> 214 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 214 Cys Ala Thr Trp Gln Cys Tyr Trp His Glu Tyr Gly 1 5 10 <210> 215 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 215 Cys Lys Thr Trp Thr Cys Tyr Trp His Glu Phe Gly 1 5 10 <210> 216 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 216 Cys Thr Thr Trp Thr Cys Tyr Trp His Gln Tyr Gly 1 5 10 <210> 217 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 217 Cys Arg Thr Trp Glu Cys Tyr Trp His Glu Phe Gly 1 5 10 <210> 218 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 218 Cys Arg Thr Trp Gln Cys Tyr Trp His Glu Tyr Gly 1 5 10 <210> 219 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 219 Cys Gln Thr Trp Gln Cys Tyr Trp Arg Glu Asn Gly 1 5 10 <210> 220 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 220 Cys Arg Thr Trp Glu Cys Tyr Trp His Glu Tyr Gly 1 5 10 <210> 221 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 221 Cys Thr Thr Trp Glu Cys Tyr Trp His Glu Tyr Gly 1 5 10 <210> 222 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 222 Cys Arg Thr Trp Glu Cys Tyr Trp His Glu Gln Ser 1 5 10 <210> 223 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 223 Cys Thr Thr Trp Glu Cys Tyr Trp His Gln Phe Gly 1 5 10 <210> 224 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 224 Cys Thr Thr Trp Glu Cys Tyr Trp His Glu Phe Gly 1 5 10 <210> 225 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 225 Cys Gln Thr Trp Glu Cys Tyr Trp His Leu Tyr Gly 1 5 10 <210> 226 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 226 Cys Glu Asp Trp Lys Cys Tyr Trp His Lys Tyr Gly 1 5 10 <210> 227 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 227 Cys Thr Asp Trp Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 228 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 228 Cys Ala Asp Trp Val Cys Tyr Trp His Thr Tyr Gly 1 5 10 <210> 229 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 229 Cys Ala Asp Trp Val Cys Tyr Trp His Arg His Ala Asp Arg Val Lys 1 5 10 15 <210> 230 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 230 Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Glu Arg 1 5 10 <210> 231 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 231 Cys Ala Asp Trp Val Cys Tyr Trp His Thr His Gly Glu Arg 1 5 10 <210> 232 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 232 Asp Thr Pro Arg Cys Arg Thr Trp Glu Cys Tyr Trp His Thr Phe Gly 1 5 10 15 <210> 233 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 233 Cys Gln Thr Trp Val Cys Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 234 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 234 Cys Gln Thr Trp Gln Cys Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 235 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 235 Cys Gln Thr Trp Gln Cys Tyr Trp Arg Thr Asn Gly Xaa Lys 1 5 10 <210> 236 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 236 Cys Gln Thr Trp Gln Cys Tyr Trp Arg Lys Asn Gly Xaa Lys 1 5 10 <210> 237 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 237 Cys Gln Thr Trp Gln Cys Tyr Trp Arg Arg Asn Gly Xaa Lys 1 5 10 <210> 238 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (10) <223> Dapa <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 238 Cys Gln Thr Trp Gln Cys Tyr Trp Arg Xaa Asn Gly Xaa Lys 1 5 10 <210> 239 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (10) <223> Orn <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 239 Cys Gln Thr Trp Gln Cys Tyr Trp Arg Xaa Asn Gly Xaa Lys 1 5 10 <210> 240 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 240 Cys Arg Thr Trp Gln Cys Tyr Trp Arg Lys Phe Gly Xaa Lys 1 5 10 <210> 241 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Arg <400> 241 Cys Gln Thr Trp Gln Cys Tyr Trp Arg Glu Asn Gly Xaa Arg 1 5 10 <210> 242 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 242 Cys Gln Thr Trp Gln Cys Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 243 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 243 Cys Gln Asp Trp Gln Cys Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 244 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 244 Cys Gln Thr Trp Gln Cys Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 245 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 245 Cys Gln Thr Trp Gln Cys Tyr Trp Arg Thr Asn Gly Xaa Lys 1 5 10 <210> 246 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 246 Cys Gln Thr Trp Val Cys Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 247 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 247 Cys Gln Thr Trp Gln Cys Tyr Trp Arg Lys Asn Gly Xaa Lys 1 5 10 <210> 248 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> Cav <400> 248 Cys Gln Thr Trp Gln Cys Tyr Trp Xaa Glu Asn Gly 1 5 10 <210> 249 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> Cpa <400> 249 Cys Gln Thr Trp Gln Cys Tyr Trp Xaa Glu Asn Gly 1 5 10 <210> 250 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 250 Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 251 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 251 Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 252 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys-Ac <400> 252 Cys Gln Thr Trp Gln Cys Tyr Trp Arg Lys Asn Gly 1 5 10 <210> 253 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 253 Cys Arg Thr Trp Gln Cys Tyr Trp Arg Lys Phe Gly 1 5 10 <210> 254 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-Me-Lys <400> 254 Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 255 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 255 Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 256 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLeu <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 256 Xaa Gln Thr Trp Gln Xaa Phe Xaa Leu Lys Asn Asn 1 5 10 <210> 257 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-CONH2) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 257 Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Asn 1 5 10 <210> 258 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 258 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 259 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4- (2-aminoethoxy) <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 259 Xaa Gln Thr Trp Gln Cys Phe Trp Lys Glu Asn Gly 1 5 10 <210> 260 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> 4-amino-4-carboxy-tetrahydropyran <400> 260 Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Glu Asn Asn 1 5 10 <210> 261 <211> 20 <212> PRT <213> Mus sp. <400> 261 Asn Trp Gln Pro Trp Ser Ser Pro Phe Val His Gln Thr Ser Gln Glu 1 5 10 15 Thr Gly Lys Arg             20 <210> 262 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 262 Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 263 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 263 Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 264 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (2) (2) <223> Any amino acid <220> <221> MOD_RES &Lt; 222 > (3) <223> Any amino acid <220> <221> MOD_RES &Lt; 222 > (5) <223> Any amino acid <400> 264 Cys Xaa Xaa Trp Xaa Cys Tyr Trp 1 5 <210> 265 <211> 4 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> alpha-MeLys <400> 265 Lys Glu Asn Gly One <210> 266 <211> 4 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> alpha-MeLys <220> <221> MOD_RES <222> (2) (2) <223> Lys (Ac) <400> 266 Lys Lys Asn Asn One <210> 267 <211> 4 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> alpha-MeLeu <220> <221> MOD_RES <222> (2) (2) <223> Lys (Ac) <400> 267 Leu Lys Asn Asn One <210> 268 <211> 4 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> alpha-MeLeu <400> 268 Leu Glu Asn Gly One <210> 269 <211> 4 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> alpha-MeLeu <400> 269 Leu Glu Asn Gly One <210> 270 <211> 4 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> alpha-MeLys <400> 270 Lys Glu Asn Asn One <210> 271 <211> 6 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (5) <223> 2-Nal <220> <221> MOD_RES <222> (6) <223> alpha-MeLys <400> 271 Trp Gln Cys Tyr Xaa Lys 1 5 <210> 272 <211> 6 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (4) (4) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (5) <223> 2-Nal <220> <221> MOD_RES <222> (6) <223> alpha-MeLys <400> 272 Trp Gln Cys Phe Xaa Lys 1 5 <210> 273 <211> 6 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (4) (4) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (5) <223> 2-Nal <220> <221> MOD_RES <222> (6) <223> Aib <400> 273 Trp Gln Cys Phe Xaa Xaa 1 5 <210> 274 <211> 6 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (3) <223> Pen <220> <221> MOD_RES <222> (4) (4) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (5) <223> 2-Nal <220> <221> MOD_RES <222> (6) <223> alpha-MeLys <400> 274 Trp Gln Xaa Phe Xaa Lys 1 5 <210> 275 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (2) (2) <223> Any amino acid <220> <221> MOD_RES &Lt; 222 > (3) <223> Any amino acid <220> <221> MOD_RES &Lt; 222 > (5) <223> Any amino acid <220> <221> MOD_RES &Lt; 222 > (10) <223> Any amino acid <220> <221> MOD_RES (12). (12) <223> Any amino acid <220> <221> MOD_RES &Lt; 222 > (13) <223> Any amino acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 275 Cys Xaa Xaa Trp Xaa Cys Tyr Trp His Xaa Phe Xaa Xaa Lys 1 5 10 <210> 276 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Tyr (OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 276 Xaa Gln Thr Trp Gln Cys Tyr Xaa Lys Glu Asn Gly 1 5 10 <210> 277 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 277 Phe Pro Thr Trp Glu Trp Tyr Trp Cys Asn Arg Asp 1 5 10 <210> 278 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 278 Ala Leu Thr Trp Glu Phe Tyr Trp Leu Cys Arg Glu 1 5 10 <210> 279 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Tyr (OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 279 Xaa Gln Thr Trp Gln Xaa Tyr Xaa Lys Glu Asn Gly 1 5 10 <210> 280 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 280 Xaa Gln Thr Trp Gln Cys Phe Trp Lys Glu Asn Gly 1 5 10 <210> 281 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 281 Lys Met Thr Trp Gln Asp Tyr Trp Leu Tyr Gly Arg 1 5 10 <210> 282 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-Me-Lys <400> 282 Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 283 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 283 Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 284 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 284 Ala Met Thr Trp Gln Asp Tyr Trp Leu Tyr Gly Lys 1 5 10 <210> 285 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLeu <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 285 Xaa Gln Thr Trp Gln Xaa Phe Xaa Leu Lys Asn Asn 1 5 10 <210> 286 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-CONH2) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 286 Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Asn 1 5 10 <210> 287 <400> 287 000 <210> 288 <400> 288 000 <210> 289 <400> 289 000 <210> 290 <400> 290 000 <210> 291 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Beta-Ala <400> 291 Ala Ser Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 292 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> D-Lys <400> 292 Lys Ser Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 293 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> D-Lys <220> <221> MOD_RES <222> (2) (2) <223> Beta-Ala <400> 293 Lys Ala Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 294 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) (2-aminoethoxy) acetic acid <400> 294 Xaa Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 295 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> D-Lys <400> 295 Lys Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 296 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 296 Cys Lys Asp Trp Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 297 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 297 Cys Ala Asp Trp Lys Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 298 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 298 Cys Ala Asp Trp Val Cys Tyr Trp Lys Thr Phe Gly 1 5 10 <210> 299 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 299 Cys Ala Asp Trp Val Cys Tyr Trp His Lys Phe Gly 1 5 10 <210> 300 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 300 Cys Ala Asp Trp Val Cys Tyr Trp His Thr Lys Gly 1 5 10 <210> 301 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 301 Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Asp Lys 1 5 10 <210> 302 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 302 Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Asp Lys 1 5 10 <210> 303 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (13) <223> Beta-Ala <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 303 Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Ala Lys 1 5 10 <210> 304 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 304 Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Xaa Lys 1 5 10 <210> 305 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 305 Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Lys 1 5 10 <210> 306 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Beta-Ala <400> 306 Ala Ser Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 307 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> D-Lys <400> 307 Lys Ser Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 308 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> D-Lys <220> <221> MOD_RES <222> (2) (2) <223> Beta-Ala <400> 308 Lys Ala Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 309 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) (2-aminoethoxy) acetic acid <400> 309 Xaa Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 310 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> D-Lys <400> 310 Lys Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 311 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 311 Cys Lys Asp Trp Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 312 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 312 Cys Ala Asp Trp Lys Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 313 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 313 Cys Ala Asp Trp Val Cys Tyr Trp Lys Thr Phe Gly 1 5 10 <210> 314 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 314 Cys Ala Asp Trp Val Cys Tyr Trp His Lys Phe Gly 1 5 10 <210> 315 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 315 Cys Ala Asp Trp Val Cys Tyr Trp His Thr Lys Gly 1 5 10 <210> 316 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES (12). (12) <223> D-Lys <400> 316 Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Lys 1 5 10 <210> 317 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (13) <223> D-Lys <400> 317 Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Lys 1 5 10 <210> 318 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (13) <223> Beta-Ala <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 318 Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Ala Lys 1 5 10 <210> 319 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 319 Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Xaa Lys 1 5 10 <210> 320 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 320 Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Lys 1 5 10 <210> 321 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (8) <223> Beta-hTyr <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 321 Cys Gln Thr Trp Gln Cys Tyr Tyr Arg Val Asn Gly Xaa Lys 1 5 10 <210> 322 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (8) Beta-hPhe (4-F) <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 322 Cys Gln Thr Trp Gln Cys Tyr Phe Arg Val Asn Gly Xaa Lys 1 5 10 <210> 323 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (8) <223> Beta-Nva (5-Phenyl) <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 323 Cys Gln Thr Trp Gln Cys Tyr Xaa Arg Val Asn Gly Xaa Lys 1 5 10 <210> 324 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe (3,4-Cl2) <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 324 Cys Gln Thr Trp Gln Cys Tyr Phe Arg Val Asn Gly Xaa Lys 1 5 10 <210> 325 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (8) <223> Tqa <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 325 Cys Gln Thr Trp Gln Cys Tyr Xaa Arg Val Asn Gly Xaa Lys 1 5 10 <210> 326 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (10) <223> Beta-hLeu <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 326 Cys Gln Thr Trp Gln Cys Tyr Trp Arg Leu Asn Gly Xaa Lys 1 5 10 <210> 327 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (10) <223> Aib <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 327 Cys Gln Thr Trp Gln Cys Tyr Trp Arg Xaa Asn Gly Xaa Lys 1 5 10 <210> 328 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (10) <223> Beta-hala <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 328 Cys Gln Thr Trp Gln Cys Tyr Trp Arg Ala Asn Gly Xaa Lys 1 5 10 <210> 329 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (10) <223> Beta-hVal <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 329 Cys Gln Thr Trp Gln Cys Tyr Trp Arg Val Asn Gly Xaa Lys 1 5 10 <210> 330 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (10) <223> Beta-spiral-pip <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 330 Cys Gln Thr Trp Gln Cys Tyr Trp Arg Xaa Asn Gly Xaa Lys 1 5 10 <210> 331 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (10) <223> Beta-Glu <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 331 Cys Gln Thr Trp Gln Cys Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 332 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> Beta-hLeu <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 332 Cys Gln Thr Trp Gln Cys Tyr Trp Leu Val Asn Gly Xaa Lys 1 5 10 <210> 333 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> Beta-Aib <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 333 Cys Gln Thr Trp Gln Cys Tyr Trp Xaa Val Asn Gly Xaa Lys 1 5 10 <210> 334 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> Beta-hala <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 334 Cys Gln Thr Trp Gln Cys Tyr Trp Ala Val Asn Gly Xaa Lys 1 5 10 <210> 335 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> Beta-hVal <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 335 Cys Gln Thr Trp Gln Cys Tyr Trp Val Val Asn Gly Xaa Lys 1 5 10 <210> 336 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> Beta-spiral-pip <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 336 Cys Gln Thr Trp Gln Cys Tyr Trp Xaa Val Asn Gly Xaa Lys 1 5 10 <210> 337 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> Beta-hArg <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 337 Cys Gln Thr Trp Gln Cys Tyr Trp Arg Val Asn Gly Xaa Lys 1 5 10 <210> 338 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (6) <223> MeCys <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 338 Met Arg Thr Trp Gln Cys Tyr Trp Arg Lys Phe Gly Xaa Lys 1 5 10 <210> 339 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 339 Ala Cys Asp Trp Val Cys Tyr Trp Arg Lys Phe Gly Xaa Lys 1 5 10 <210> 340 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 340 Ser Arg Thr Trp Gln Ser Tyr Trp Arg Lys Phe Gly Xaa Lys 1 5 10 <210> 341 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES (12). (12) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (13) <223> D-Lys <400> 341 Cys Asp Trp Val Cys Tyr Trp Arg Lys Phe Gly Xaa Lys 1 5 10 <210> 342 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (6) <223> MeCys <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 342 Ala Arg Thr Trp Gln Cys Tyr Trp Arg Lys Phe Gly Xaa Lys 1 5 10 <210> 343 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 343 Ala Arg Thr Trp Gln Ala Tyr Trp Arg Lys Phe Gly Xaa Lys 1 5 10 <210> 344 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <220> <221> MOD_RES (12). (12) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (13) <223> D-Lys <400> 344 Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Xaa Lys 1 5 10 <210> 345 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 345 Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly Xaa Lys 1 5 10 <210> 346 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 346 Cys Ser Thr Trp Glu Cys Tyr Trp Arg Val Tyr Gly Xaa Lys 1 5 10 <210> 347 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (2) (2) <223> Orn <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 347 Cys Xaa Thr Trp Gln Cys Tyr Trp Arg Val Phe Gly Xaa Lys 1 5 10 <210> 348 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> Orn <220> <221> MOD_RES &Lt; 222 > (10) <223> Dap <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 348 Cys Gln Thr Trp Gln Cys Tyr Trp Xaa Xaa Phe Gly Xaa Lys 1 5 10 <210> 349 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (2) (2) <223> N-MeAsn <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 349 Cys Asn Thr Trp Gln Cys Tyr Trp Arg Val Phe Gly Xaa Lys 1 5 10 <210> 350 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (2) (2) <223> N-MeLys <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 350 Cys Lys Thr Trp Gln Cys Tyr Trp Arg Val Phe Gly Xaa Lys 1 5 10 <210> 351 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (2) (2) <223> Dab <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 351 Cys Xaa Thr Trp Gln Cys Tyr Trp Arg Val Phe Gly Xaa Lys 1 5 10 <210> 352 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> Orn <220> <221> MOD_RES &Lt; 222 > (10) <223> Dap <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 352 Cys Gln Thr Trp Gln Cys Tyr Tyr Xaa Xaa Phe Gly Xaa Lys 1 5 10 <210> 353 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> Orn <220> <221> MOD_RES &Lt; 222 > (10) <223> Dap <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 353 Cys Ser Thr Trp Gln Cys Tyr Trp Xaa Xaa Tyr Gly Xaa Lys 1 5 10 <210> 354 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> Cit <220> <221> MOD_RES &Lt; 222 > (10) <223> Dap <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 354 Cys Ser Thr Trp Glu Cys Tyr Trp Xaa Xaa Tyr Gly Xaa Lys 1 5 10 <210> 355 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> Orn <220> <221> MOD_RES &Lt; 222 > (10) <223> Dap <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 355 Cys Gln Thr Trp Gln Cys Phe Phe Xaa Xaa Phe Gly Xaa Lys 1 5 10 <210> 356 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 356 Cys Pro Thr Trp Gln Cys Tyr Trp Arg Val Phe Gly Xaa Lys 1 5 10 <210> 357 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> Orn <220> <221> MOD_RES &Lt; 222 > (10) <223> Dab <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 357 Cys Ser Thr Trp Glu Cys Tyr Trp Xaa Xaa Tyr Gly Xaa Lys 1 5 10 <210> 358 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 358 Cys Ser Thr Trp Glu Cys Tyr Trp Arg Val Phe Gly Xaa Lys 1 5 10 <210> 359 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 359 Cys Leu Thr Trp Gln Cys Tyr Trp Arg Val Phe Gly Xaa Lys 1 5 10 <210> 360 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> Orn <220> <221> MOD_RES &Lt; 222 > (10) <223> Dap <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 360 Cys Gln Thr Trp Gln Cys Tyr Phe Xaa Xaa Phe Gly Xaa Lys 1 5 10 <210> 361 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 361 Cys Asn Thr Trp Gln Cys Tyr Trp Arg Val Phe Gly Xaa Lys 1 5 10 <210> 362 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (2) (2) <223> Dap <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 362 Cys Xaa Thr Trp Gln Cys Tyr Trp Arg Val Phe Gly Xaa Lys 1 5 10 <210> 363 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (2) (2) <223> N-Me-Ala <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 363 Cys Ala Thr Trp Gln Cys Tyr Trp Arg Val Phe Gly Xaa Lys 1 5 10 <210> 364 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 364 Cys Lys Thr Trp Gln Cys Tyr Trp Arg Val Phe Gly Xaa Lys 1 5 10 <210> 365 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (10) <223> Cha <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 365 Cys Gln Asp Trp Gln Cys Tyr Trp Arg Xaa Phe Gly Xaa Lys 1 5 10 <210> 366 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (10) <223> Ogl <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 366 Cys Gln Thr Trp Gln Cys Tyr Trp Arg Xaa Phe Gly Xaa Lys 1 5 10 <210> 367 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (10) <223> Dap <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 367 Cys Gln Thr Trp Gln Cys Tyr Trp Lys Xaa Phe Gly Xaa Lys 1 5 10 <210> 368 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (10) <223> Dap <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 368 Cys Gln Thr Trp Gln Cys Tyr Trp His Xaa Phe Gly Xaa Lys 1 5 10 <210> 369 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 369 Cys Gln Thr Trp Gln Cys Tyr Trp Arg Leu Phe Gly Xaa Lys 1 5 10 <210> 370 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hArg <220> <221> MOD_RES &Lt; 222 > (10) <223> Dap <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 370 Cys Gln Thr Trp Gln Cys Tyr Trp Arg Xaa Phe Gly Xaa Lys 1 5 10 <210> 371 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 371 Cys Ser Thr Trp Glu Cys Tyr Trp Arg Thr Phe Gly 1 5 10 <210> 372 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 372 Cys Asp Ser Trp Glu Cys Tyr Trp Arg Thr Tyr Gly 1 5 10 <210> 373 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 373 Cys Ser Thr Trp Glu Cys Tyr Trp His Thr Tyr Gly 1 5 10 <210> 374 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 374 Cys Lys Thr Trp Thr Cys Tyr Trp His Thr Tyr Gly 1 5 10 <210> 375 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 375 Cys Arg Thr Trp Glu Cys Tyr Trp His Glu Tyr Ser 1 5 10 <210> 376 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 376 Cys Arg Thr Trp Thr Cys Tyr Trp His Glu Tyr Gly 1 5 10 <210> 377 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 377 Cys Phe Thr Trp Gln Cys Tyr Trp His Glu Tyr Ser 1 5 10 <210> 378 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> 3-Pal <400> 378 Cys Gln Thr Trp Gln Cys Tyr Trp Xaa Glu Asn Gly 1 5 10 <210> 379 <211> 6 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 379 Cys Gln Thr Trp Gln Cys 1 5 <210> 380 <211> 6 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 380 Cys Arg Thr Trp Gln Cys 1 5 <210> 381 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 381 Cys Ala Asp Trp Val Cys Tyr 1 5 <210> 382 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 382 Cys Ala Asp Trp Val Cys Tyr Trp 1 5 <210> 383 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 383 Cys Ala Asp Trp Val Cys Tyr Trp His 1 5 <210> 384 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 384 Cys Ala Asp Trp Val Cys Tyr Trp His Thr 1 5 10 <210> 385 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 385 Cys Ala Asp Trp Val Cys Tyr Trp His Thr Phe 1 5 10 <210> 386 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 386 Cys Met Thr Trp Gln Cys Tyr Trp Leu Tyr Gly Arg 1 5 10 <210> 387 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 387 Cys Arg Thr Trp Gln Cys Tyr Trp His Glu Phe Gly 1 5 10 <210> 388 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 388 Cys Arg Thr Trp Glu Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 389 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 389 Cys Gln Thr Trp Gln Cys Tyr Trp His Glu Phe Gly 1 5 10 <210> 390 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 390 Cys Arg Thr Trp Gln Cys Tyr Trp Gln Gln Phe Gly Gly Glu 1 5 10 <210> 391 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 391 Cys Arg Ser Trp Gln Cys Tyr Trp Leu Asn Phe Gly Pro Asp 1 5 10 <210> 392 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 392 Cys Arg Thr Trp Gln Cys Tyr Trp Leu Lys Met Gly Asp Ser 1 5 10 <210> 393 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 393 Cys Gln Thr Trp Gln Cys Tyr Trp Ile Lys Arg Asp Gln Gly 1 5 10 <210> 394 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 394 Cys Ser Thr Trp Gln Cys Tyr Trp Leu Lys His Gly Gly Glu 1 5 10 <210> 395 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 395 Cys Ser Thr Trp Glu Cys Tyr Trp Ser Gln Arg Ala Asp Gln 1 5 10 <210> 396 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 396 Cys Gln Thr Trp Glu Cys Tyr Trp Arg Thr Phe Gly Pro Ser 1 5 10 <210> 397 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 397 Cys Arg Thr Trp Gln Cys Tyr Trp Gln Glu Lys Gly Thr Asp 1 5 10 <210> 398 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 398 Cys Gln Thr Trp Gln Cys Tyr Trp Leu Asp Ser Leu Gly Asp 1 5 10 <210> 399 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 399 Cys Arg Thr Trp Gln Cys Tyr Trp Thr Lys Phe Gly Ser Glu Pro 1 5 10 15 <210> 400 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu   <400> 400 Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Pro Gly 1 5 10 <210> 401 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu   <400> 401 Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Leu Gly 1 5 10 <210> 402 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu   <400> 402 Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Thr Gly 1 5 10 <210> 403 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu   <400> 403 Cys Gln Thr Trp Gln Cys Tyr Trp Leu Phe Asn Gly 1 5 10 <210> 404 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu   <400> 404 Cys Gln Thr Trp Gln Cys Tyr Trp Leu Pro Asn Gly 1 5 10 <210> 405 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu   <400> 405 Cys Gln Thr Trp Gln Cys Tyr Trp Leu Asn Asn Gly 1 5 10 <210> 406 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu   <400> 406 Cys Gln Thr Trp Gln Cys Tyr Trp Leu Leu Asn Gly 1 5 10 <210> 407 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu   <400> 407 Cys Gln Thr Trp Gln Cys Tyr Trp Leu Thr Asn Gly 1 5 10 <210> 408 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 408 Cys Gln Thr Trp Gln Cys Tyr Trp Phe Glu Asn Gly 1 5 10 <210> 409 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 409 Cys Gln Thr Trp Gln Cys Tyr Trp Pro Glu Asn Gly 1 5 10 <210> 410 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 410 Cys Gln Thr Trp Gln Cys Tyr Trp Gln Glu Asn Gly 1 5 10 <210> 411 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 411 Cys Gln Thr Trp Gln Cys Tyr Trp Thr Glu Asn Gly 1 5 10 <210> 412 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide &Lt; 400 > 412 Cys Gln Thr Trp Gln Cys Tyr Trp Glu Glu Asn Gly 1 5 10 <210> 413 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 413 Cys Gln Thr Trp Phe Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 414 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 414 Cys Gln Thr Trp Pro Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 415 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 415 Cys Gln Thr Trp Asn Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 416 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 416 Cys Gln Thr Trp Arg Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 417 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 417 Cys Gln Thr Trp Thr Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 418 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 418 Cys Gln Thr Trp Glu Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 419 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 419 Cys Gln Thr Gly Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 420 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 420 Cys Gln Thr Pro Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 421 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 421 Cys Gln Thr Asn Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 422 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 422 Cys Gln Thr Arg Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 423 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 423 Cys Gln Thr Thr Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 424 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 424 Cys Gln Thr Glu Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 425 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 425 Cys Gln Phe Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 426 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 426 Cys Gln Pro Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 427 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 427 Cys Gln Asn Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 428 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 428 Cys Gln Arg Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 429 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 429 Cys Gln Glu Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 430 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 430 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 431 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeOrn <400> 431 Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Glu Asn Gly 1 5 10 <210> 432 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-CO2H) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 432 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 433 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 433 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 434 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-CONH2) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 434 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 435 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 435 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Ala 1 5 10 <210> 436 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 436 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Ala Glu 1 5 10 <210> 437 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 437 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 438 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4- (2-aminoethoxy) <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 438 Xaa Gln Thr Trp Gln Cys Phe Trp Lys Glu Asn Gly 1 5 10 <210> 439 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 439 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Asp Asn Gly 1 5 10 <210> 440 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (succinic acid) &Lt; 400 > 440 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 441 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (glutaric acid) <400> 441 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 442 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (pyroglutamic acid) conjugated through side chain <400> 442 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 443 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (isovaleric acid) <400> 443 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 444 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <220> <221> MOD_RES &Lt; 222 > (13) <223> D-Lys <400> 444 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly Lys 1 5 10 <210> 445 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <400> 445 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly Xaa 1 5 10 <210> 446 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <400> 446 Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Gln Asn Gly 1 5 10 <210> 447 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 447 Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Lys Asn Ala 1 5 10 <210> 448 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <400> 448 Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Lys Asn Gly 1 5 10 <210> 449 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 449 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 450 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 450 Cys Phe Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 451 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 451 Cys Pro Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 452 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 452 Cys Asn Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 453 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 453 Cys Gly Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 454 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 454 Cys Thr Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 455 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 455 Cys Glu Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 456 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> N-MeLeu <400> 456 Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 457 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeOrn <400> 457 Cys Gln Thr Trp Gln Cys Tyr Trp Xaa Glu Asn Gly 1 5 10 <210> 458 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeOrn <400> 458 Cys Gln Thr Trp Gln Cys Tyr Trp Xaa Glu Asn Gly 1 5 10 <210> 459 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (7) (7) <223> alpha-MePhe <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 459 Cys Gln Thr Trp Gln Cys Phe Trp Leu Glu Asn Gly 1 5 10 <210> 460 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib &Lt; 400 > 460 Cys Gln Thr Trp Gln Cys Tyr Trp Xaa Glu Asn Gly 1 5 10 <210> 461 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (7) (7) <223> hTyr <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 461 Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 462 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (7) (7) <223> Beep <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 462 Cys Gln Thr Trp Gln Cys Xaa Trp Leu Glu Asn Gly 1 5 10 <210> 463 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> Ogl <400> 463 Cys Gln Thr Trp Gln Cys Tyr Trp Xaa Glu Asn Gly 1 5 10 <210> 464 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 464 Cys Gln Thr Trp Gln Cys Tyr Trp Leu Lys Asn Gly 1 5 10 <210> 465 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 465 Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly Gly 1 5 10 <210> 466 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 466 Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly Pro 1 5 10 <210> 467 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 467 Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly Glu 1 5 10 <210> 468 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <220> <221> MOD_RES &Lt; 222 > (13) <223> D-Glu <400> 468 Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly Glu 1 5 10 <210> 469 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (8) <223> alpha-MePhe <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 469 Cys Gln Thr Trp Gln Cys Tyr Phe Leu Glu Asn Gly 1 5 10 <210> 470 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 470 Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly Pro 1 5 10 <210> 471 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 471 Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly Gly 1 5 10 <210> 472 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 472 Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly Leu 1 5 10 <210> 473 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 473 Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly Phe 1 5 10 <210> 474 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 474 Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly Glu 1 5 10 <210> 475 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 475 Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly Asn 1 5 10 <210> 476 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 476 Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly Thr 1 5 10 <210> 477 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 477 Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly Arg 1 5 10 <210> 478 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (10) <223> hLeu <400> 478 Pro Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 479 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (10) <223> hLeu <400> 479 Leu Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 480 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (10) <223> hLeu &Lt; 400 > 480 Phe Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 481 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (10) <223> hLeu <400> 481 Glu Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 482 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (10) <223> hLeu <400> 482 Asn Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 483 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (10) <223> hLeu <400> 483 Arg Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 484 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 484 Cys Gln Thr Trp Gln Cys Tyr Xaa Leu Glu Asn Gly 1 5 10 <210> 485 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (8) <223> 1-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 485 Cys Gln Thr Trp Gln Cys Tyr Xaa Leu Glu Asn Gly 1 5 10 <210> 486 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (7) (7) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 486 Cys Gln Thr Trp Gln Cys Xaa Trp Leu Glu Asn Gly 1 5 10 <210> 487 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (7) (7) <223> 1-Nal <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 487 Cys Gln Thr Trp Gln Cys Xaa Xaa Leu Glu Asn Gly 1 5 10 <210> 488 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (7) (7) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (8) <223> 1-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 488 Cys Gln Thr Trp Gln Cys Xaa Xaa Leu Glu Asn Gly 1 5 10 <210> 489 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (7) (7) <223> Aic <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 489 Cys Gln Thr Trp Gln Cys Xaa Trp Leu Glu Asn Gly 1 5 10 <210> 490 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 490 Cys Gln Thr Trp Gln Cys His Trp Leu Glu Asn Gly 1 5 10 <210> 491 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 491 Cys Gln Thr Trp Gln Cys Tyr His Leu Glu Asn Gly 1 5 10 <210> 492 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (7) (7) <223> Tyr (OMe) <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 492 Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 493 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (8) <223> Beep <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 493 Cys Gln Thr Trp Gln Cys Tyr Xaa Leu Glu Asn Gly 1 5 10 <210> 494 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (8) <223> Tyr (OMe) <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 494 Cys Gln Thr Trp Gln Cys Tyr Tyr Leu Glu Asn Gly 1 5 10 <210> 495 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 495 Cys Gln Thr Trp Gln Cys His His Leu Glu Asn Gly 1 5 10 <210> 496 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (8) <223> alpha-MeTrp <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 496 Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Gln Gly 1 5 10 <210> 497 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (5) <223> Lys (PEG8) <400> 497 Cys Gln Thr Trp Lys Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 498 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> Any amino acid <400> 498 Cys Gln Thr Trp Gln Cys Tyr Trp Xaa Leu Asn Gly 1 5 10 <210> 499 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (5) <223> Lys (PEG8) <220> <221> MOD_RES &Lt; 222 > (9) <223> Lys (PEG8) <400> 499 Cys Gln Thr Trp Lys Cys Tyr Trp Lys Glu Asn Gly 1 5 10 <210> 500 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (5) <223> Lys (Palm) <400> 500 Cys Gln Thr Trp Lys Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 501 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> Orn <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Palm) <400> 501 Cys Gln Thr Trp Gln Cys Tyr Trp Xaa Lys Asn Gly 1 5 10 <210> 502 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (2) (2) <223> D-Asn <220> <221> MOD_RES &Lt; 222 > (3) <223> D-Glu <220> <221> MOD_RES <222> (4) (4) <223> D-Leu <220> <221> MOD_RES &Lt; 222 > (5) <223> D-Trp <220> <221> MOD_RES <222> (6) <223> D-Tyr <220> <221> MOD_RES <222> (7) (7) <223> D-Cys <220> <221> MOD_RES &Lt; 222 > (8) <223> D-Gln <220> <221> MOD_RES &Lt; 222 > (9) <223> D-Trp <220> <221> MOD_RES &Lt; 222 > (10) <223> D-Thr <220> <221> MOD_RES &Lt; 222 > (11) <223> D-Gln <220> <221> MOD_RES (12). (12) <223> D-Cys <400> 502 Gly Asn Glu Leu Trp Tyr Cys Gln Trp Thr Gln Cys 1 5 10 <210> 503 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> Orn <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (PEG8) <400> 503 Cys Gln Thr Trp Gln Cys Tyr Trp Xaa Lys Asn Gly 1 5 10 <210> 504 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 504 Cys Arg Thr Trp Gln Cys Tyr Trp His Glu Phe Gly 1 5 10 <210> 505 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 505 Cys Arg Thr Trp Glu Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 506 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 506 Cys Gln Thr Trp Gln Cys Tyr Trp His Glu Phe Gly 1 5 10 <210> 507 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 507 Cys Gln Thr Trp Gln Cys Tyr Trp Arg Asn Phe Gly Asp Ser 1 5 10 <210> 508 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 508 Cys Gln Thr Trp Gln Cys Tyr Trp Arg Asn Phe Glu Ser Gly 1 5 10 <210> 509 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 509 Cys Gln Asp Trp Gln Cys Tyr Trp Arg Glu Phe Gly Pro Gly 1 5 10 <210> 510 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 510 Cys Gln Asp Trp Gln Cys Tyr Trp Arg Ser Phe Gly Pro Gln 1 5 10 <210> 511 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 511 Cys Gln Thr Trp Gln Cys Tyr Trp Arg Thr Leu Gly Pro Ser 1 5 10 <210> 512 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> D-Pro <400> 512 Cys Gln Thr Trp Gln Cys Tyr Trp Pro Glu Asn Gly 1 5 10 <210> 513 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 513 Cys Gln Thr Trp Gln Cys Tyr Trp Glu Leu Asn Gly 1 5 10 <210> 514 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 514 Cys Gln Thr Trp Glu Cys Tyr Trp Glu Leu Asn Gly 1 5 10 <210> 515 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (8) <223> 1-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLeu <400> 515 Cys Gln Thr Trp Gln Cys Tyr Xaa Leu Glu Asn Gly 1 5 10 <210> 516 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (8) <223> 1-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> D-Asn <400> 516 Cys Gln Thr Trp Gln Cys Tyr Xaa Asn Glu Asn Gly 1 5 10 <210> 517 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (11) <223> Lys (Palm) <400> 517 Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Lys Gly 1 5 10 <210> 518 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES (12). (12) <223> Lys (Palm) <400> 518 Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Lys 1 5 10 <210> 519 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 519 Cys Ser Thr Trp Glu Cys Tyr Trp Arg Thr Phe Gly 1 5 10 <210> 520 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 520 Cys Asp Ser Trp Glu Cys Tyr Trp Arg Thr Tyr Gly 1 5 10 <210> 521 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 521 Cys Ser Thr Trp Glu Cys Tyr Trp His Thr Tyr Gly 1 5 10 <210> 522 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 522 Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 523 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 523 Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 524 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-Me-Leu <400> 524 Xaa Gln Thr Trp Gln Xaa Phe Xaa Leu Gln Asn Asn 1 5 10 <210> 525 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-Me-Leu <400> 525 Xaa Gln Thr Trp Gln Xaa Phe Xaa Leu Gln Asn Asn 1 5 10 <210> 526 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 526 Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Gln 1 5 10 <210> 527 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 527 Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Gln 1 5 10 <210> 528 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeVal <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <220> <221> MOD_RES &Lt; 222 > (13) <223> D-Lys <400> 528 Xaa Gln Thr Trp Gln Xaa Phe Xaa Val Lys Asn Asn Lys 1 5 10 <210> 529 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-acetylaminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeVal <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <220> <221> MOD_RES &Lt; 222 > (13) <223> D-Lys <400> 529 Xaa Gln Thr Trp Gln Xaa Phe Xaa Val Lys Asn Asn Lys 1 5 10 <210> 530 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-acetylaminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeVal &Lt; 400 > 530 Xaa Gln Thr Trp Gln Xaa Phe Xaa Val Lys Asn Asn 1 5 10 <210> 531 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-acetylaminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 531 Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Asn 1 5 10 <210> 532 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 532 Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Asn 1 5 10 <210> 533 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> alpha-MeLys <220> <221> MOD_RES <222> (2) (2) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Pen <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe (4-CONH2) <220> <221> MOD_RES &Lt; 222 > (9) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (10) <223> alpha-MeVal <220> <221> MOD_RES &Lt; 222 > (11) <223> Lys (Ac) <400> 533 Lys Xaa Gln Thr Trp Gln Xaa Phe Xaa Val Lys Asn Asn 1 5 10 <210> 534 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-CONH2) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 534 Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Asn 1 5 10 <210> 535 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-CONH2) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <400> 535 Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 536 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-CONH2) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> 4-amino-4-carboxy-tetrahydropyran <400> 536 Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 537 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-CONH2) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Achc <400> 537 Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 538 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-CONH2) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Acvc <400> 538 Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 539 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-CONH2) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLeu <400> 539 Xaa Asn Thr Trp Gln Xaa Phe Xaa Leu Lys Asn Asn 1 5 10 <210> 540 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib &Lt; 400 > 540 Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 541 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> 4-amino-4-carboxy-tetrahydropyran <400> 541 Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 542 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Achc <400> 542 Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 543 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Acvc <400> 543 Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 544 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLeu <400> 544 Xaa Asn Thr Trp Gln Xaa Phe Xaa Leu Lys Asn Asn 1 5 10 <210> 545 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-CONH2) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 545 Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Asn 1 5 10 <210> 546 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-CONH2) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 546 Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Asn 1 5 10 <210> 547 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 547 Xaa Arg Thr Trp Gln Xaa Tyr Trp Arg Lys Phe Gly Xaa Lys 1 5 10 <210> 548 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (2) (2) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 548 Ala Xaa Asp Trp Val Xaa Tyr Trp Arg Lys Phe Gly Xaa Lys 1 5 10 <210> 549 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 549 Xaa Gln Thr Trp Gln Xaa Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 550 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES &Lt; 222 > (9) <223> N-MeArg <400> 550 Xaa Gln Thr Trp Gln Xaa Tyr Trp Arg Glu Asn Gly 1 5 10 <210> 551 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 551 Xaa Gln Thr Trp Gln Xaa Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 552 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES &Lt; 222 > (9) <223> N-MeArg <400> 552 Xaa Gln Thr Trp Gln Xaa Tyr Trp Arg Glu Asn Gly 1 5 10 <210> 553 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (2) (2) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES &Lt; 222 > (9) <223> Orn <220> <221> MOD_RES &Lt; 222 > (10) <223> Dap <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 553 Ala Xaa Asp Trp Val Xaa Tyr Trp Xaa Xaa Phe Gly Xaa Lys 1 5 10 <210> 554 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLeu <400> 554 Xaa Gln Thr Trp Gln Xaa Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 555 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES &Lt; 222 > (9) <223> D-Asn <400> 555 Xaa Gln Thr Trp Gln Xaa Tyr Trp Asn Glu Asn Gly 1 5 10 <210> 556 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 556 Xaa Gln Thr Trp Gln Xaa Tyr Xaa Lys Glu Asn Gly 1 5 10 <210> 557 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 557 Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 558 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 558 Xaa Gln Thr Trp Gln Xaa Xaa Xaa Lys Glu Asn Gly 1 5 10 <210> 559 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeOrn <400> 559 Xaa Gln Thr Trp Gln Xaa Tyr Xaa Xaa Glu Asn Gly 1 5 10 <210> 560 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeOrn &Lt; 400 > 560 Xaa Gln Thr Trp Gln Xaa Tyr Trp Xaa Glu Asn Gly 1 5 10 <210> 561 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES &Lt; 222 > (8) <223> 1-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeOrn <400> 561 Xaa Gln Thr Trp Gln Xaa Tyr Xaa Xaa Glu Asn Gly 1 5 10 <210> 562 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeOrn <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 562 Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Gly 1 5 10 <210> 563 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 563 Xaa Gln Thr Trp Gln Xaa Tyr Trp Lys Lys Asn Gly 1 5 10 <210> 564 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe- (4-OMe) <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 564 Xaa Gln Thr Trp Gln Xaa Phe Trp Lys Lys Asn Gly 1 5 10 <210> 565 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 565 Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 566 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 1-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 566 Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 567 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Beep <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 567 Xaa Gln Thr Trp Gln Xaa Xaa Xaa Lys Lys Asn Gly 1 5 10 <210> 568 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (3,4-Cl2) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 568 Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 569 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (3,5-F2) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 569 Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 570 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-NH2) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 570 Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 571 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (8) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (9) <223> Lys (Ac) <400> 571 Xaa Gln Thr Trp Gln Xaa Xaa Lys Lys Asn Gly 1 5 10 <210> 572 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (3,4-Cl2) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeOrn <400> 572 Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Glu Asn Gly 1 5 10 <210> 573 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-CN) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeOrn <400> 573 Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Glu Asn Gly 1 5 10 <210> 574 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (3,5-F2) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeOrn <400> 574 Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Glu Asn Gly 1 5 10 <210> 575 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-CH2CO2H) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeOrn <400> 575 Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Glu Asn Gly 1 5 10 <210> 576 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-CH2COEt2) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeOrn <400> 576 Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Glu Asn Gly 1 5 10 <210> 577 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (penta-F) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeOrn <400> 577 Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Glu Asn Gly 1 5 10 <210> 578 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-CF3) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 578 Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 579 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 579 Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 580 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys &Lt; 400 > 580 Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 581 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (ivDde) <400> 581 Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 582 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 582 Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 583 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 583 Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 584 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 584 Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 585 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> PyroGlu <220> <221> MOD_RES <222> (2) (2) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Pen <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (9) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (10) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (11) <223> Lys (Ac) <400> 585 Glu Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 586 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 586 Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 587 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 587 Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 588 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 588 Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 589 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 589 Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 590 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 590 Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 591 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <400> 591 Xaa Ala Asp Trp Val Xaa Tyr Trp His Thr Phe Gly 1 5 10 <210> 592 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 592 Xaa Gly Thr Trp Gln Xaa Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 593 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 593 Xaa Thr Thr Trp Gln Xaa Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 594 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 594 Xaa Ser Thr Trp Gln Xaa Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 595 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (2) (2) <223> Dap <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 595 Xaa Xaa Thr Trp Gln Xaa Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 596 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (2) (2) <223> alpha-MeOrn <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 596 Xaa Xaa Thr Trp Gln Xaa Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 597 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 597 Xaa Asn Thr Trp Gln Xaa Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 598 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 598 Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 599 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 599 Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Asn 1 5 10 <210> 600 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 600 Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 601 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 601 Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Glu Asn Ala 1 5 10 <210> 602 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLeu <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) &Lt; 400 > 602 Xaa Gln Thr Trp Gln Xaa Phe Xaa Leu Lys Asn Asn 1 5 10 <210> 603 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLeu <400> 603 Xaa Gln Thr Trp Gln Xaa Phe Xaa Leu Gln Asn Asn 1 5 10 <210> 604 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib &Lt; 400 > 604 Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Glu Asn Asn 1 5 10 <210> 605 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 605 Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 606 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 606 Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Gln 1 5 10 <210> 607 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (2) (2) <223> Dap (Ac) <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-acetylaminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys (Ac) <400> 607 Xaa Xaa Thr Trp Gln Xaa Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 608 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (2) (2) Alpha-MeOrn (Ac) <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-acetylaminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys (Ac) <400> 608 Xaa Xaa Thr Trp Gln Xaa Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 609 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-acetylaminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys (Ac) <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 609 Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 610 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-acetylaminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys (Ac) <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 610 Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Asn 1 5 10 <210> 611 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-acetylaminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys (Ac) <400> 611 Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 612 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-acetylaminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys (Ac) <400> 612 Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Glu Asn Ala 1 5 10 <210> 613 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-acetylaminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLeu <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 613 Xaa Gln Thr Trp Gln Xaa Phe Xaa Leu Lys Asn Asn 1 5 10 <210> 614 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-acetylaminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLeu <400> 614 Xaa Gln Thr Trp Gln Xaa Phe Xaa Leu Gln Asn Asn 1 5 10 <210> 615 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-acetylaminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <400> 615 Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Glu Asn Asn 1 5 10 <210> 616 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-acetylaminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 616 Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 617 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-acetylaminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 617 Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Gln 1 5 10 <210> 618 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <400> 618 Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Glu Asn Asn 1 5 10 <210> 619 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 619 Xaa Gln Thr Trp Gln Xaa Phe Xaa Leu Glu Asn Ala 1 5 10 <210> 620 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 620 Xaa Thr Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 621 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 621 Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Ala 1 5 10 <210> 622 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 622 Xaa Thr Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Gln 1 5 10 <210> 623 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 623 Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Gln 1 5 10 <210> 624 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 624 Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Ala 1 5 10 <210> 625 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 625 Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 626 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <220> <221> MOD_RES (12). (12) <223> Beta-Ala <400> 626 Xaa Gln Thr Trp Gln Xaa Phe Xaa Leu Lys Asn Ala 1 5 10 <210> 627 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <220> <221> MOD_RES (12). (12) <223> Beta-Ala <400> 627 Xaa Gln Thr Trp Gln Xaa Phe Xaa Leu Lys Asn Ala 1 5 10 <210> 628 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <220> <221> MOD_RES (12). (12) <223> Beta-Ala <400> 628 Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Ala 1 5 10 <210> 629 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <220> <221> MOD_RES (12). (12) <223> Beta-Ala <400> 629 Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Ala 1 5 10 <210> 630 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <400> 630 Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Glu Asn Asn 1 5 10 <210> 631 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 631 Xaa Asn Thr Trp Gln Xaa Phe Xaa Leu Glu Asn Ala 1 5 10 <210> 632 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 632 Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 633 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <220> <221> MOD_RES (12). (12) <223> Beta-Ala <400> 633 Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Ala 1 5 10 <210> 634 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 634 Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Gln 1 5 10 <210> 635 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 635 Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Ala 1 5 10 <210> 636 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 636 Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Ala 1 5 10 <210> 637 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 637 Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 638 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 638 Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Gln 1 5 10 <210> 639 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <220> <221> MOD_RES (12). (12) <223> Beta-Ala <400> 639 Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Ala 1 5 10 <210> 640 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <220> <221> MOD_RES (12). (12) <223> Beta-Ala &Lt; 400 > 640 Xaa Asn Thr Trp Gln Xaa Phe Xaa Leu Lys Asn Ala 1 5 10 <210> 641 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <220> <221> MOD_RES (12). (12) <223> Beta-Ala <400> 641 Xaa Asn Thr Trp Gln Xaa Phe Xaa Leu Lys Asn Ala 1 5 10 <210> 642 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (2) (2) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Pen <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (9) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (10) <223> Aib <220> <221> MOD_RES &Lt; 222 > (11) <223> Lys (Ac) <400> 642 Glu Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 643 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> D-Asp <220> <221> MOD_RES <222> (2) (2) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Pen <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (9) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (10) <223> Aib <220> <221> MOD_RES &Lt; 222 > (11) <223> Lys (Ac) <400> 643 Asp Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 644 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (2) (2) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Pen <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (9) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (10) <223> Aib <220> <221> MOD_RES &Lt; 222 > (11) <223> Lys (Ac) <400> 644 Arg Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 645 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> D-Arg <220> <221> MOD_RES <222> (2) (2) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Pen <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (9) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (10) <223> Aib <220> <221> MOD_RES &Lt; 222 > (11) <223> Lys (Ac) <400> 645 Arg Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 646 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (2) (2) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Pen <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (9) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (10) <223> Aib <220> <221> MOD_RES &Lt; 222 > (11) <223> Lys (Ac) <400> 646 Phe Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 647 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> D-Phe <220> <221> MOD_RES <222> (2) (2) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Pen <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (9) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (10) <223> Aib <220> <221> MOD_RES &Lt; 222 > (11) <223> Lys (Ac) <400> 647 Phe Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 648 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> 2-Nal <220> <221> MOD_RES <222> (2) (2) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Pen <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (9) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (10) <223> Aib <220> <221> MOD_RES &Lt; 222 > (11) <223> Lys (Ac) <400> 648 Xaa Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 649 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (2) (2) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Pen <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (9) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (10) <223> Aib <220> <221> MOD_RES &Lt; 222 > (11) <223> Lys (Ac) <400> 649 Thr Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 650 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (2) (2) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Pen <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (9) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (10) <223> Aib <220> <221> MOD_RES &Lt; 222 > (11) <223> Lys (Ac) <400> 650 Leu Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 651 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> D-Gln <220> <221> MOD_RES <222> (2) (2) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Pen <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (9) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (10) <223> Aib <220> <221> MOD_RES &Lt; 222 > (11) <223> Lys (Ac) <400> 651 Gln Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 652 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> D-Asn <220> <221> MOD_RES <222> (2) (2) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Pen <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (9) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (10) <223> Aib <220> <221> MOD_RES &Lt; 222 > (11) <223> Lys (Ac) <400> 652 Asn Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 653 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeVal <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <220> <221> MOD_RES &Lt; 222 > (13) <223> D-Lys <400> 653 Xaa Gln Thr Trp Gln Xaa Phe Xaa Val Lys Asn Asn Lys 1 5 10 <210> 654 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-acetylaminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeVal <400> 654 Xaa Gln Thr Trp Gln Xaa Phe Xaa Val Lys Asn Asn 1 5 10 <210> 655 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-acetylaminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 655 Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Asn 1 5 10 <210> 656 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2- (acetyl-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys (Ac) <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 656 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 657 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2- (acetyl-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys (Ac) <400> 657 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 658 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> 4-amino-4-carboxy-tetrahydropyran <400> 658 Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Glu Asn Asn 1 5 10 <210> 659 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 659 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Gln 1 5 10 <210> 660 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeVal <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) &Lt; 400 > 660 Xaa Gln Thr Trp Gln Cys Phe Xaa Val Lys Asn Gly 1 5 10 <210> 661 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <220> <221> MOD_RES (12). (12) <223> Beta-Ala <400> 661 Xaa Gln Thr Trp Gln Cys Phe Xaa Leu Lys Asn Ala 1 5 10 <210> 662 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) [223] Phe [4- (2- (acetyl-aminoethoxy)]] <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys (Ac) <400> 662 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Gln 1 5 10 <210> 663 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2- (acetyl-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys (Ac) <400> 663 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Asn 1 5 10 <210> 664 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLeu <400> 664 Xaa Gln Thr Trp Gln Cys Phe Xaa Leu Glu Asn Asn 1 5 10 <210> 665 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLeu <220> <221> MOD_RES &Lt; 222 > (10) <223> Cit <400> 665 Xaa Gln Thr Trp Gln Cys Phe Xaa Leu Xaa Asn Asn 1 5 10 <210> 666 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 666 Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Asn 1 5 10 <210> 667 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> D-Lys <220> <221> MOD_RES <222> (2) (2) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Pen <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe (4-CONH2) <220> <221> MOD_RES &Lt; 222 > (9) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (10) <223> alpha-MeVal <220> <221> MOD_RES &Lt; 222 > (11) <223> Lys (Ac) <400> 667 Lys Xaa Gln Thr Trp Gln Xaa Phe Xaa Val Lys Asn Asn 1 5 10 <210> 668 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-CONH2) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 668 Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Asn 1 5 10 <210> 669 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-CONH2) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeVal <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 669 Xaa Gln Thr Trp Gln Xaa Phe Xaa Val Lys Asn Asn 1 5 10 <210> 670 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-CONH2) <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe (3,4-OMe2) <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeVal <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 670 Xaa Gln Thr Trp Gln Xaa Phe Phe Val Lys Asn Asn 1 5 10 <210> 671 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> D-Phe <220> <221> MOD_RES <222> (2) (2) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Pen <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (9) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (10) <223> Aib <220> <221> MOD_RES &Lt; 222 > (11) <223> Lys (Ac) <400> 671 Phe Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 672 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> D-Phe <220> <221> MOD_RES <222> (2) (2) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Pen <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (9) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (10) <223> 4-amino-4-carboxy-tetrahydropyran <220> <221> MOD_RES &Lt; 222 > (11) <223> Lys (Ac) <400> 672 Phe Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 673 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> D-Phe <220> <221> MOD_RES <222> (2) (2) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Pen <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (9) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (10) <223> Achc <220> <221> MOD_RES &Lt; 222 > (11) <223> Lys (Ac) <400> 673 Phe Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 674 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> D-Phe <220> <221> MOD_RES <222> (2) (2) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Pen <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (9) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (10) <223> 4-amino-4-carboxy-tetrahydropyran <220> <221> MOD_RES &Lt; 222 > (11) <223> Cit <400> 674 Phe Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Xaa Asn Asn 1 5 10 <210> 675 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> D-Phe <220> <221> MOD_RES <222> (2) (2) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Pen <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (9) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (10) <223> Achc <220> <221> MOD_RES &Lt; 222 > (11) <223> Cit <400> 675 Phe Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Xaa Asn Asn 1 5 10 <210> 676 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> D-Phe <220> <221> MOD_RES <222> (2) (2) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Pen <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (9) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (10) <223> Aib <220> <221> MOD_RES &Lt; 222 > (11) <223> Lys (Ac) <220> <221> MOD_RES &Lt; 222 > (13) <223> Beta-Ala <400> 676 Phe Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Ala 1 5 10 <210> 677 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> D-Phe <220> <221> MOD_RES <222> (2) (2) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Pen <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (9) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (10) <223> 4-amino-4-carboxy-tetrahydropyran <220> <221> MOD_RES &Lt; 222 > (11) <223> Lys (Ac) <400> 677 Phe Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 678 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> D-Phe <220> <221> MOD_RES <222> (2) (2) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Pen <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (9) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (10) <223> Achc <220> <221> MOD_RES &Lt; 222 > (11) <223> Lys (Ac) <400> 678 Phe Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 679 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> D-Phe <220> <221> MOD_RES <222> (2) (2) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Pen <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (9) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (10) <223> 4-amino-4-carboxy-tetrahydropyran <220> <221> MOD_RES &Lt; 222 > (11) <223> Cit <400> 679 Phe Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Xaa Asn Asn 1 5 10 <210> 680 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> D-Phe <220> <221> MOD_RES <222> (2) (2) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Pen <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (9) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (10) <223> Achc <220> <221> MOD_RES &Lt; 222 > (11) <223> Cit &Lt; 400 > 680 Phe Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Xaa Asn Asn 1 5 10 <210> 681 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> D-Phe <220> <221> MOD_RES <222> (2) (2) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Pen <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (9) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (10) <223> Achc <400> 681 Phe Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Glu Asn Asn 1 5 10 <210> 682 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-CONH2) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 682 Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 683 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-CONH2) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> 4-amino-4-carboxy-tetrahydropyran <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 683 Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 684 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-CONH2) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Achc <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 684 Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 685 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-CONH2) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Acpc <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 685 Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 686 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-CONH2) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLeu <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 686 Xaa Asn Thr Trp Gln Xaa Phe Xaa Leu Lys Asn Asn 1 5 10 <210> 687 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 687 Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 688 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> 4-amino-4-carboxy-tetrahydropyran <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 688 Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 689 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Achc <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 689 Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 690 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES (12). (12) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (13) <223> D-Lys <400> 690 Gln Asp Trp Gln Cys Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 691 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (5) <223> hCys <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 691 Gln Asp Trp Gln Cys Cys Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 692 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 692 Xaa Arg Thr Trp Gln Cys Tyr Trp Arg Lys Phe Gly Xaa Lys 1 5 10 <210> 693 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (6) <223> Abu <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 693 Cys Arg Thr Trp Gln Xaa Tyr Trp Arg Lys Phe Gly Xaa Lys 1 5 10 <210> 694 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 694 Xaa Gln Thr Trp Gln Cys Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 695 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 695 Xaa Arg Thr Trp Gln Xaa Tyr Trp Arg Lys Phe Gly Xaa Lys 1 5 10 <210> 696 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Abu <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 696 Xaa Arg Thr Trp Gln Xaa Tyr Trp Arg Lys Phe Gly Xaa Lys 1 5 10 <210> 697 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> D-Cys <220> <221> MOD_RES <222> (6) <223> Abu <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 697 Cys Arg Thr Trp Gln Xaa Tyr Trp Arg Lys Phe Gly Xaa Lys 1 5 10 <210> 698 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES &Lt; 222 > (9) <223> Orn <220> <221> MOD_RES &Lt; 222 > (10) <223> Dap <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 698 Xaa Gln Thr Trp Gln Cys Tyr Trp Xaa Xaa Asn Gly Xaa Lys 1 5 10 <210> 699 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 699 Xaa Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 700 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (6) <223> D-Cys <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 700 Xaa Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 701 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 701 Xaa Gln Thr Trp Gln Xaa Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 702 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 702 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 703 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLeu <400> 703 Xaa Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 704 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 704 Xaa Gln Thr Trp Gln Cys Tyr Xaa Lys Glu Asn Gly 1 5 10 <210> 705 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 705 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 706 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeOrn <400> 706 Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Glu Asn Gly 1 5 10 <210> 707 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeOrn <400> 707 Xaa Gln Thr Trp Gln Cys Phe Trp Xaa Glu Asn Gly 1 5 10 <210> 708 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 708 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 709 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 709 Xaa Gln Thr Trp Gln Cys Phe Trp Lys Lys Asn Gly 1 5 10 <210> 710 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 710 Xaa Gln Thr Trp Gln Cys Phe Trp Lys Glu Asn Gly 1 5 10 <210> 711 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 1-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 711 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 712 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 712 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 713 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeOrn <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 713 Xaa Gln Thr Trp Gln Cys Tyr Trp Xaa Lys Asn Gly 1 5 10 <210> 714 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> D-Asn <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 714 Xaa Gln Thr Trp Gln Cys Phe Xaa Asn Lys Asn Gly 1 5 10 <210> 715 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-Phenoxy) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 715 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 716 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) HPhe (3,4-dimethoxy) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 716 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 717 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> DMT <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 717 Xaa Gln Thr Trp Gln Cys Xaa Xaa Lys Lys Asn Gly 1 5 10 <210> 718 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-CONH2) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 718 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 719 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (3,4-Cl2) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 719 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 720 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 720 Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 721 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 721 Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 722 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 722 Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 723 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) Trp (2,5,7-tri-tert-Butyl) <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 723 Xaa Gln Thr Trp Gln Cys Phe Trp Lys Glu Asn Gly 1 5 10 <210> 724 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe (4-Oallyl) <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 724 Xaa Gln Thr Trp Gln Cys Phe Phe Lys Glu Asn Gly 1 5 10 <210> 725 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) Tyr (3-tBu) <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 725 Xaa Gln Thr Trp Gln Cys Phe Tyr Lys Glu Asn Gly 1 5 10 <210> 726 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe (4-tBu) <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 726 Xaa Gln Thr Trp Gln Cys Phe Phe Lys Glu Asn Gly 1 5 10 <210> 727 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe (4-guanidino) <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 727 Xaa Gln Thr Trp Gln Cys Phe Phe Lys Glu Asn Gly 1 5 10 <210> 728 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe (Bzl) <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 728 Xaa Gln Thr Trp Gln Cys Phe Phe Lys Glu Asn Gly 1 5 10 <210> 729 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) Tyr (3-tBu) <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 729 Xaa Gln Thr Trp Gln Cys Tyr Trp Lys Glu Asn Gly 1 5 10 <210> 730 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Acpc <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 730 Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 731 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLeu <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 731 Xaa Asn Thr Trp Gln Xaa Phe Xaa Leu Lys Asn Asn 1 5 10 <210> 732 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> N-MeAla <220> <221> MOD_RES (12). (12) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (13) <223> D-Lys <400> 732 Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Xaa Lys 1 5 10 <210> 733 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> N-MeAla <220> <221> MOD_RES &Lt; 222 > (5) <223> Pen <220> <221> MOD_RES (12). (12) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (13) <223> D-Lys <400> 733 Ala Asp Trp Val Xaa Tyr Trp His Thr Phe Gly Xaa Lys 1 5 10 <210> 734 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> N-MeAla <220> <221> MOD_RES &Lt; 222 > (5) <223> D-Pen <220> <221> MOD_RES (12). (12) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (13) <223> D-Lys <400> 734 Ala Asp Trp Val Xaa Tyr Trp His Thr Phe Gly Xaa Lys 1 5 10 <210> 735 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> N-MeAla <220> <221> MOD_RES &Lt; 222 > (5) <223> hCys <220> <221> MOD_RES (12). (12) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (13) <223> D-Lys <400> 735 Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Xaa Lys 1 5 10 <210> 736 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES (12). (12) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (13) <223> D-Lys <400> 736 Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Xaa Lys 1 5 10 <210> 737 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (5) <223> Pen <220> <221> MOD_RES (12). (12) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (13) <223> D-Lys <400> 737 Ala Asp Trp Val Xaa Tyr Trp His Thr Phe Gly Xaa Lys 1 5 10 <210> 738 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (5) <223> D-Pen <220> <221> MOD_RES (12). (12) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (13) <223> D-Lys <400> 738 Ala Asp Trp Val Xaa Tyr Trp His Thr Phe Gly Xaa Lys 1 5 10 <210> 739 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (5) <223> hCys <220> <221> MOD_RES (12). (12) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (13) <223> D-Lys <400> 739 Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Xaa Lys 1 5 10 <210> 740 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES (12). (12) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (13) <223> D-Lys <400> 740 Gln Asp Trp Gln Cys Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 741 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES (12). (12) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (13) <223> D-Lys <400> 741 Gln Asp Trp Gln Cys Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 742 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES (12). (12) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (13) <223> D-Lys <400> 742 Gln Asp Trp Gln Cys Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 743 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES (12). (12) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (13) <223> D-Lys <400> 743 Gln Asp Trp Gln Cys Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 744 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES (12). (12) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (13) <223> D-Lys <400> 744 Gln Asp Trp Gln Cys Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 745 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES (12). (12) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (13) <223> D-Lys <400> 745 Gln Asp Trp Gln Cys Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 746 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (5) <223> hCys <220> <221> MOD_RES (12). (12) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (13) <223> D-Lys <400> 746 Gln Asp Trp Gln Cys Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 747 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (5) <223> hCys <220> <221> MOD_RES (12). (12) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (13) <223> D-Lys <400> 747 Gln Asp Trp Gln Cys Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 748 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (5) <223> hCys <220> <221> MOD_RES (12). (12) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (13) <223> D-Lys <400> 748 Gln Asp Trp Gln Cys Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 749 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (5) <223> hCys <220> <221> MOD_RES (12). (12) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (13) <223> D-Lys <400> 749 Gln Asp Trp Gln Cys Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 750 <400> 750 000 <210> 751 <400> 751 000 <210> 752 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLeu <220> <221> MOD_RES (12). (12) <223> Beta-Ala <400> 752 Xaa Gln Thr Trp Gln Cys Phe Xaa Leu Gln Asn Ala 1 5 10 <210> 753 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Acbc <400> 753 Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Glu Asn Asn 1 5 10 <210> 754 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Achc <400> 754 Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Glu Asn Asn 1 5 10 <210> 755 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)]] <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Acvc <400> 755 Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Glu Asn Asn 1 5 10 <210> 756 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeVal <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <220> <221> MOD_RES &Lt; 222 > (13) <223> D-Lys <400> 756 Xaa Gln Thr Trp Gln Xaa Phe Xaa Val Lys Asn Asn Lys 1 5 10 <210> 757 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-acetylaminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeVal <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <220> <221> MOD_RES &Lt; 222 > (13) <223> D-Lys <400> 757 Xaa Gln Thr Trp Gln Xaa Phe Xaa Val Lys Asn Asn Lys 1 5 10 <210> 758 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-acetylaminoethoxy)]] <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeVal <400> 758 Xaa Gln Thr Trp Gln Xaa Phe Xaa Val Lys Asn Asn 1 5 10 <210> 759 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-acetylaminoethoxy)]] <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 759 Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Asn 1 5 10 <210> 760 <211> 629 <212> PRT <213> Homo sapiens <400> 760 Met Asn Gln Val Thr Ile Gln Trp Asp Ala Val Ile Ala Leu Tyr Ile 1 5 10 15 Leu Phe Ser Trp Cys His Gly Gly Ile Thr Asn Ile Asn Cys Ser Gly             20 25 30 His Ile Trp Val Glu Pro Ala Thr Ile Phe Lys Met Gly Met Asn Ile         35 40 45 Ser Ile Tyr Cys Gln Ala Ala Ile Lys Asn Cys Gln Pro Arg Lys Leu     50 55 60 His Phe Tyr Lys Asn Gly Ile Lys Glu Arg Phe Gln Ile Thr Arg Ile 65 70 75 80 Asn Lys Thr Thr Ala Arg Leu Trp Tyr Lys Asn Phe Leu Glu Pro His                 85 90 95 Ala Ser Met Tyr Cys Thr Ala Glu Cys Pro Lys His Phe Gln Glu Thr             100 105 110 Leu Ile Cys Gly Lys Asp Ile Ser Ser Gly Tyr Pro Pro Asp Ile Pro         115 120 125 Asp Glu Val Thr Cys Val Ile Tyr Glu Tyr Ser Gly Asn Met Thr Cys     130 135 140 Thr Trp Asn Ala Gly Lys Leu Thr Tyr Ile Asp Thr Lys Tyr Val Val 145 150 155 160 His Val Lys Ser Leu Glu Thr Glu Glu Glu Gln Gln Tyr Leu Thr Ser                 165 170 175 Ser Tyr Ile Asn Ile Ser Thr Asp Ser Leu Gln Gly Gly Lys Lys Tyr             180 185 190 Leu Val Trp Val Gln Ala Asn Ala Leu Gly Met Glu Glu Ser Lys         195 200 205 Gln Leu Gln Ile His Leu Asp Asp Ile Val Ile Pro Ser Ala Ala Val     210 215 220 Ile Ser Arg Ala Glu Thr Ile Asn Ala Thr Val Pro Lys Thr Ile Ile 225 230 235 240 Tyr Trp Lys Ser Gln Thr Thr Ile Glu Lys Val Ser Cys Glu Met Arg                 245 250 255 Tyr Lys Ala Thr Thr Asn Gln Thr Trp Asn Val Lys Glu Phe Asp Thr             260 265 270 Asn Phe Thr Tyr Val Gln Gln Ser Glu Phe Tyr Leu Glu Pro Asn Ile         275 280 285 Lys Tyr Val Phe Gln Val Arg Cys Gln Glu Thr Gly Lys Arg Tyr Trp     290 295 300 Gln Pro Trp Ser Ser Leu Phe Phe His Lys Thr Pro Glu Thr Val Pro 305 310 315 320 Gln Val Thr Ser Lys Ala Phe Gln His Asp Thr Trp Asn Ser Gly Leu                 325 330 335 Thr Val Ala Ser Ile Ser Thr Gly His Leu Thr Ser Asp Asn Arg Gly             340 345 350 Asp Ile Gly Leu Leu Leu Gly Met Ile Val Phe Ala Val Met Leu Ser         355 360 365 Ile Leu Ser Leu Ile Gly Ile Phe Asn Arg Ser Phe Arg Thr Gly Ile     370 375 380 Lys Arg Arg Ile Leu Leu Leu Ile Pro Lys Trp Leu Tyr Glu Asp Ile 385 390 395 400 Pro Asn Met Lys Asn Ser Asn Val Val Lys Met Leu Gln Glu Asn Ser                 405 410 415 Glu Leu Met Asn Asn As Ser Ser Glu Gln Val Leu Tyr Val Asp Pro             420 425 430 Met Ile Thr Glu Ile Lys Glu Ile Phe Ile Pro Glu His Lys Pro Thr         435 440 445 Asp Tyr Lys Lys Glu Asn Thr Gly Pro Leu Glu Thr Arg Asp Tyr Pro     450 455 460 Gln Asn Ser Leu Phe Asp Asn Thr Th Val Val Tyr Ile Pro Asp Leu 465 470 475 480 Asn Thr Gly Tyr Lys Pro Gln Ile Ser Asn Phe Leu Pro Glu Gly Ser                 485 490 495 His Leu Ser Asn Asn Asn Glu Ile Thr Ser Leu Thr Leu Lys Pro Pro             500 505 510 Val Asp Ser Leu Asp Ser Gly Asn Asn Pro Arg Leu Gln Lys His Pro         515 520 525 Asn Phe Ala Phe Ser Val Ser Ser Val Asn Ser Leu Ser Asn Thr Ile     530 535 540 Phe Leu Gly Glu Leu Ser Leu Ile Leu Asn Gln Gly Glu Cys Ser Ser 545 550 555 560 Pro Asp Ile Gln Asn Ser Val Glu Glu Glu Thr Thr Met Leu Leu Glu                 565 570 575 Asn Asp Ser Pro Ser Glu Thr Ile Pro Glu Gln Thr Leu Leu Pro Asp             580 585 590 Glu Phe Val Ser Cys Leu Gly Ile Val Asn Glu Glu Leu Pro Ser Ile         595 600 605 Asn Thr Tyr Phe Pro Gln Asn Ile Leu Glu Ser His Phe Asn Arg Ile     610 615 620 Ser Leu Leu Glu Lys 625 <210> 761 <211> 659 <212> PRT <213> Mus musculus <400> 761 Met Lys Arg Glu Arg Glu Met Arg Gly Phe Tyr Tyr Ile Trp Asp Met 1 5 10 15 Ser His Leu Thr Leu Gln Leu His Val Val Ile Ala Leu Tyr Val Leu             20 25 30 Phe Arg Trp Cys His Gly Gly Ile Thr Ser Ile Asn Cys Ser Gly Asp         35 40 45 Met Trp Val Glu Pro Gly Glu Ile Phe Gln Met Gly Met Asn Val Ser     50 55 60 Ile Tyr Cys Gln Glu Ala Leu Lys His Cys Arg Pro Arg Asn Leu Tyr 65 70 75 80 Phe Tyr Lys Asn Gly Phe Lys Glu Glu Phe Asp Ile Thr Arg Ile Asn                 85 90 95 Arg Thr Thr Ala Arg Ile Trp Tyr Lys Gly Phe Ser Glu Pro His Ala             100 105 110 Tyr Met His Cys Thr Ala Glu Cys Pro Gly His Phe Gln Glu Thr Leu         115 120 125 Ile Cys Gly Lys Asp Ile Ser Ser Gly Tyr Pro Pro Asp Ala Pro Ser     130 135 140 Asn Leu Thr Cys Val Ile Tyr Glu Tyr Ser Gly Asn Met Thr Cys Thr 145 150 155 160 Trp Asn Thr Gly Lys Pro Thr Tyr Ile Asp Thr Lys Tyr Ile Val His                 165 170 175 Val Lys Ser Leu Glu Thr Glu Glu Glu Gln Gln Tyr Leu Ala Ser Ser             180 185 190 Tyr Val Lys Ile Ser Thr Asp Ser Leu Gln Gly Gly Lys Lys Tyr Leu         195 200 205 Val Trp Val Gln Ala Val Asn Ser Leu Gly Met Glu Asn Ser Gln Gln     210 215 220 Leu His Val His Leu Asp Asp Ile Val Ile Pro Ser Ala Ser Ile Ile 225 230 235 240 Ser Arg Ala Glu Thr Thr Asn Asp Thr Val Pro Lys Thr Ile Ile Tyr                 245 250 255 Trp Lys Ser Lys Thr Met Ile Glu Lys Val Phe Cys Glu Met Arg Tyr             260 265 270 Lys Thr Thr Thr Asn Gln Thr Trp Ser Val Lys Glu Phe Asp Ala Asn         275 280 285 Phe Thr Tyr Val Gln Gln Ser Glu Phe Tyr Leu Glu Pro Asp Ser Lys     290 295 300 Tyr Val Phe Gln Val Arg Cys Gln Glu Thr Gly Lys Arg Asn Trp Gln 305 310 315 320 Pro Trp Ser Ser Pro Phe Val His Gln Thr Ser Gln Glu Thr Gly Lys                 325 330 335 Arg Asn Trp Gln Pro Trp Ser Ser Pro Phe Val His Gln Thr Ser Gln             340 345 350 Thr Val Ser Gln Val Thr Ala Lys Ser Ser His Glu Pro Gln Lys Met         355 360 365 Glu Met Leu Ser Ala Thr Ile Phe Arg Gly His Pro Ala Ser Gly Asn     370 375 380 His Gln Asp Ile Gly Leu Leu Ser Gly Met Val Phe Leu Ala Ile Met 385 390 395 400 Leu Pro Ile Phe Ser Leu Ile Gly Ile Phe Asn Arg Ser Leu Arg Ile                 405 410 415 Gly Ile Lys Arg Lys Val Leu Leu Met Ile Pro Lys Trp Leu Tyr Glu             420 425 430 Asp Ile Pro Asn Met Glu Asn Ser Asn Val Ala Lys Leu Leu Gln Glu         435 440 445 Lys Ser Val Phe Glu Asn Asp Asn Ala Ser Glu Gln Ala Leu Tyr Val     450 455 460 Asp Pro Val Leu Thr Glu Ile Ser Glu Ile Ser Pro Leu Glu His Lys 465 470 475 480 Pro Thr Asp Tyr Lys Glu Glu Arg Leu Thr Gly Leu Leu Glu Thr Arg                 485 490 495 Asp Cys Pro Leu Gly Met Leu Ser Thr Ser Ser Val Val Tyr Ile             500 505 510 Pro Asp Leu Asn Thr Gly Tyr Lys Pro Gln Val Ser Asn Val Pro Pro         515 520 525 Gly Gly Asn Leu Phe Ile Asn Arg Asp Glu Arg Asp Pro Thr Ser Leu     530 535 540 Glu Thr Asp Asp His Phe Ala Arg Leu Lys Thr Tyr Pro Asn Phe 545 550 555 560 Gln Phe Ser Ala Ser Ser Ae Leu Leu Asn Lys Thr Leu Ile Leu                 565 570 575 Asp Glu Leu Cys Leu Val Leu Asn Gln Gly Glu Phe Asn Ser Leu Asp             580 585 590 Ile Lys Asn Ser Arg Gln Glu Glu Thr Ser Ile Val Leu Gln Ser Asp         595 600 605 Ser Pro Ser Glu Thr Ile Pro Ala Gln Thr Leu Leu Ser Asp Glu Phe     610 615 620 Val Ser Cys Leu Ala Ile Gly Asn Glu Asp Leu Pro Ser Ile Asn Ser 625 630 635 640 Tyr Phe Pro Gln Asn Val Leu Glu Ser His Phe Ser Arg Ile Ser Leu                 645 650 655 Phe Gln Lys              <210> 762 <211> 639 <212> PRT <213> Rattus norvegicus <400> 762 Met Arg Arg Glu Arg Glu Met Arg Gly Phe Tyr Tyr Ile Trp Asp Met 1 5 10 15 Ser His Val Ala Leu Gln Leu His Val Val Ile Ala Leu Tyr Ala Leu             20 25 30 Phe Arg Trp Gly His Gly Gly Ile Ala Thr Ile Asn Cys Ser Gly Asn         35 40 45 Met Trp Val Glu Pro Gly Glu Ile Phe Gln Met Gly Met Asn Val Ser     50 55 60 Val Tyr Cys Gln Glu Ala Leu Lys Asn Cys Arg Pro Arg Asn Leu His 65 70 75 80 Phe Tyr Lys Asn Gly Phe Lys Glu Arg Phe His Ile Thr Arg Ile Asn                 85 90 95 Arg Thr Thr Ala Arg Val Trp Thr Lys Gly Phe Ser Glu Pro His Ala             100 105 110 Ser Met Tyr Cys Thr Ala Glu Cys Pro Gly Arg Phe Gln Glu Thr Leu         115 120 125 Ile Cys Gly Lys Asp Ile Ser Ser Gly Tyr Pro Pro Asp Ala Pro Ser     130 135 140 Asn Met Thr Cys Val Ile Tyr Glu Tyr Ser Gly Asn Met Thr Cys Thr 145 150 155 160 Trp Asn Thr Gly Lys Pro Thr Tyr Ile Asp Thr Lys Tyr Thr Val His                 165 170 175 Val Lys Ser Leu Glu Thr Glu Glu Gln Gln Gln Tyr Leu Ala Ser Asn             180 185 190 Tyr Val Asn Ile Ser Thr Asp Ser Leu Gln Gly Gly Lys Lys Tyr Leu         195 200 205 Val Trp Val Gln Ala Val Asn Ala Leu Gly Met Glu Asn Ser Gln Gln     210 215 220 Leu Gln Val His Leu Asp Asp Ile Val Ile Pro Ser Ser Ser Ile Ile 225 230 235 240 Ser Arg Ala Glu Thr Thr Asn Ala Asn Val Lys Thr Ile Ile Tyr                 245 250 255 Trp Lys Ser Lys Ile Met Thr Gly Lys Val Phe Cys Glu Met Arg Tyr             260 265 270 Lys Ala Thr Thr Asn Gln Thr Trp Asn Val Lys Glu Phe Asp Thr Asn         275 280 285 Phe Thr Tyr Val Gln Gln Ser Glu Phe Tyr Leu Glu Pro Asn Ser Lys     290 295 300 Tyr Val Phe Gln Val Arg Cys Gln Gly Thr Gly Lys Arg Tyr Trp Gln 305 310 315 320 Pro Trp Ser Ser Pro Phe Val His Gln Thr Pro Gln Thr Ala Ser Gln                 325 330 335 Val Thr Ser Lys Pro Pro His Glu Pro Gln Lys Ile Glu Met Leu Thr             340 345 350 Ala Thr Ile Phe Lys Gly His Thr Ser Asp Asn Ser Gln Asp Ile         355 360 365 Gly Leu Leu Ser Gly Met Val Phe Leu Ala Ile Met Leu Pro Ile Phe     370 375 380 Ser Leu Ile Gly Ile Phe Asn Arg Ser Leu Arg Ile Gly Ile Lys Arg 385 390 395 400 Lys Val Leu Leu Met Ile Pro Lys Trp Leu Tyr Glu Asp Ile Pro Asn                 405 410 415 Met Glu Asn Ser Asn Ile Ala Lys Leu Leu Gln Glu Lys Ser Val Phe             420 425 430 Glu Asn Glu Asn Ala Ser Glu Gln Ala Leu Tyr Val Asp Pro Ile Leu         435 440 445 Thr Glu Ile Ser Glu Ile Ser Pro Leu Glu His Lys Pro Thr Asp Tyr     450 455 460 Lys Lys Asp Arg Leu Thr Gly Phe Leu Glu Thr Arg Asp Cys Pro Leu 465 470 475 480 Thr Thr Ser Ser Ser Ser Ser Ser Val Val Tyr Ile Pro Asp Leu Asn                 485 490 495 Thr Gly Tyr Lys Pro Gln Val Ser Asn Val Pro Pro Glu Glu Asn His             500 505 510 Phe Ile Asn Arg Asp Glu Arg Asp Pro Met Ser Leu Glu Ala Thr Gly         515 520 525 Asp His Phe Ala Arg Leu Lys Thr Tyr Pro Asn Phe Thr Phe Ser Ala     530 535 540 Ser Ser Met Thr Ser Leu Ser Lys Thr Leu Ile Leu Asp Glu Leu Ser 545 550 555 560 Leu Val Leu Asn Gln Gly Glu Phe Asn Ser Leu Asp Ile Gln Asn Ser                 565 570 575 Arg Gln Glu Glu Thr Ser Met Ile Leu Gln Asn Ser Ser Ser Ser             580 585 590 Thr Ile Pro Val Gln Thr Leu Leu Pro Asp Glu Phe Val Ser Cys Leu         595 600 605 Ala Ile Gly Ser Glu Asp Leu Pro Ser Ile Asn Ser Tyr Phe Pro Gln     610 615 620 Asn Val Leu Glu Ser His Phe Ser Gly Ile Pro Leu Leu Gln Lys 625 630 635 <210> 763 <211> 629 <212> PRT <213> Pan sp. <400> 763 Met Asn Gln Val Thr Ile Gln Trp Asp Ala Val Ile Ala Leu Tyr Ile 1 5 10 15 Leu Phe Ser Trp Cys His Gly Gly Ile Thr Asn Ile Asn Cys Ser Gly             20 25 30 His Ile Trp Val Glu Pro Ala Thr Ile Phe Lys Met Gly Met Asn Ile         35 40 45 Ser Ile Tyr Cys Gln Ala Ala Ile Lys Asn Cys Gln Pro Arg Lys Leu     50 55 60 His Phe Tyr Lys Asn Gly Ile Lys Glu Arg Phe Gln Ile Thr Arg Ile 65 70 75 80 Asn Lys Thr Thr Ala Arg Leu Trp Tyr Lys Asn Phe Leu Glu Pro His                 85 90 95 Ala Ser Met Tyr Cys Thr Ala Glu Cys Pro Lys His Phe Gln Glu Thr             100 105 110 Leu Ile Cys Gly Lys Asp Ile Ser Ser Gly Tyr Pro Pro Asp Ile Pro         115 120 125 Asp Glu Val Thr Cys Val Ile Tyr Glu Tyr Ser Gly Asn Met Thr Cys     130 135 140 Thr Trp Asn Ala Gly Lys Leu Thr Tyr Met Asp Thr Lys Tyr Val Val 145 150 155 160 His Val Lys Ser Leu Glu Thr Glu Glu Glu Gln Gln Tyr Leu Thr Ser                 165 170 175 Ser Tyr Ile Asn Ile Ser Thr Asp Ser Leu Gln Gly Gly Lys Lys Tyr             180 185 190 Leu Val Trp Val Gln Ala Asn Ala Leu Gly Met Glu Glu Ser Lys         195 200 205 Gln Leu Gln Ile Tyr Leu Asp Asp Ile Val Ile Pro Ser Ala Ser Val     210 215 220 Ile Ser Arg Ala Glu Thr Ile Asn Ala Thr Val Pro Lys Thr Ile Ile 225 230 235 240 Tyr Trp Asp Ser Gln Thr Thr Ile Glu Lys Val Ser Cys Glu Met Arg                 245 250 255 Tyr Lys Ala Thr Thr Asn Gln Thr Trp Asn Val Lys Glu Phe Asp Thr             260 265 270 Asn Phe Thr Tyr Val Gln Gln Ser Glu Phe Tyr Leu Glu Pro Asn Ile         275 280 285 Lys Tyr Val Phe Gln Val Arg Cys Gln Glu Thr Gly Lys Arg Tyr Trp     290 295 300 Gln Pro Trp Ser Ser Pro Phe Phe His Lys Thr Pro Glu Thr Val Pro 305 310 315 320 Gln Val Thr Ser Lys Ala Phe Gln His Asp Thr Trp Asn Ser Gly Leu                 325 330 335 Thr Val Ala Ser Ile Ser Thr Gly His Leu Thr Ser Asp Asn Arg Gly             340 345 350 Asp Ile Gly Leu Leu Leu Gly Met Ile Val Phe Ala Val Met Leu Ser         355 360 365 Ile Leu Ser Leu Ile Gly Ile Phe Asn Arg Ser Leu Arg Thr Gly Ile     370 375 380 Lys Arg Arg Ile Leu Leu Leu Ile Pro Lys Trp Leu Tyr Glu Asp Ile 385 390 395 400 Pro Asn Met Lys Asn Ser Asn Val Val Lys Met Leu Gln Glu Asn Ser                 405 410 415 Glu Leu Met Asn Asn As Ser Ser Glu Gln Val Leu Tyr Val Asp Pro             420 425 430 Met Ile Thr Glu Ile Lys Glu Ile Phe Ile Pro Glu His Lys Pro Thr         435 440 445 Asp Tyr Lys Lys Leu Asn Thr Gly Pro Leu Glu Thr Arg Asp Thr Leu     450 455 460 Gln Asn Ser Leu Phe Asp Asn Thr Th Val Val Tyr Ile Pro Asp Leu 465 470 475 480 Asn Thr Gly Tyr Lys Pro Gln Ile Ser Asn Phe Leu Pro Glu Gly Ser                 485 490 495 His Leu Ser Asn Asn Asn Glu Ile Thr Ser Leu Thr Leu Lys Pro Pro             500 505 510 Val Asp Ser Leu Asp Ser Gly Asn Asn Pro Arg Leu Gln Lys His Pro         515 520 525 Asn Phe Ala Phe Ser Val Ser Ser Val Asn Ser Leu Ser Asn Thr Ile     530 535 540 Phe Leu Gly Glu Leu Ser Leu Ile Leu Asn Gln Gly Glu Cys Ser Ser 545 550 555 560 Pro Asp Ile Gln Asn Ser Val Glu Glu Glu Thr Thr Thr Leu Leu Glu                 565 570 575 Asn Asp Ser Pro Ser Glu Thr Ile Pro Glu Gln Thr Leu Leu Pro Asp             580 585 590 Glu Phe Val Ser Cys Leu Gly Ile Val Asn Glu Glu Leu Pro Ser Ile         595 600 605 Asn Thr Tyr Phe Pro Gln Asn Ile Leu Glu Ser His Phe Asn Arg Ile     610 615 620 Ser Leu Leu Glu Lys 625 <210> 764 <211> 631 <212> PRT <213> Canis familiaris <400> 764 Met Asn Gln Ile Thr Ile Gln Trp Asp Val Val Ile Ala Leu Tyr Ile 1 5 10 15 Phe Phe Asn Trp Cys His Gly Gly Ile Thr Asn Ile Asn Cys Ser Gly             20 25 30 His Ile Trp Val Glu Pro Ala Thr Ile Phe Lys Met Gly Met Asn Ile         35 40 45 Ser Ile Tyr Cys Gln Ala Ala Ile Lys Asn Cys Gln Pro Arg Lys Leu     50 55 60 Tyr Phe Tyr Lys Asn Gly Ile Lys Glu Arg Phe Gln Ile Thr Arg Ile 65 70 75 80 Asn Lys Thr Thr Ala Arg Leu Trp Tyr Ser Asn Phe Leu Glu Pro His                 85 90 95 Ala Ser Met Tyr Cys Thr Ala Glu Cys Pro Gly Tyr Pro Gln Glu Thr             100 105 110 Leu Ile Cys Gly Lys Asp Ile Ser Ser Gly Tyr Pro Pro Asp Val Pro         115 120 125 Asp Lys Val Thr Cys Val Ile Tyr Glu Tyr Ser Gly Asn Met Thr Cys     130 135 140 Thr Trp Asn Ser Gly Lys Pro Thr Tyr Ile Asp Thr Lys Tyr Val Val 145 150 155 160 Tyr Val Lys Ser Leu Glu Lys Glu Glu Glu Gln Gln Tyr Leu Ser Ser                 165 170 175 Ser Tyr Ile Asn Ile Ser Thr Asp Ser Leu Gln Gly Gly Lys Lys Tyr             180 185 190 Leu Val Trp Val Gln Ala Asn Ala Leu Gly Met Glu Lys Ser Lys         195 200 205 Gln Leu Gln Ile Asn Leu Asp Asp Ile Val Ile Pro Ser Ala Ala Ile     210 215 220 Ile Ser Arg Ala Glu Asp Ile Asn Thr Thr Ile Pro Lys Thr Ile Ile 225 230 235 240 His Trp Asn Ser Gln Thr Thr Ile Glu Asn Val Ser Cys Glu Met Arg                 245 250 255 His Lys Thr Thr Thr Asn Gln Thr Trp Lys Val Lys Glu Phe Asp Thr             260 265 270 Asn Phe Pro Tyr Glu Gln Gln Ser Glu Phe Tyr Leu Glu Pro Asn Thr         275 280 285 Lys Tyr Ile Phe Gln Val Arg Cys Gln Glu Thr Gly Lys Arg Tyr Trp     290 295 300 Gln Pro Trp Ser Ser Pro Phe Phe His Lys Thr Ala Glu Thr Val Pro 305 310 315 320 Gln Val Thr Val Lys Ser Phe Gln His Asp Thr Gln Asn Ser Glu Leu                 325 330 335 Leu Ile Ala Ser Ile Phe Lys Gly His Leu Thr Ser Asp Asn Arg Gln             340 345 350 Gln Asp Ile Gly Leu Leu Leu Gly Met Ile Phe Phe Ala Ala Met Leu         355 360 365 Ser Ile Leu Ser Leu Ile Gly Ile Phe Asn Arg Ser Ile Arg Thr Gly     370 375 380 Ile Lys Arg Arg Ile Leu Leu Leu Ile Pro Lys Trp Leu His Glu Asp 385 390 395 400 Ile Pro Asn Met Glu Asn Ser Lys Val Val Glu Met Leu Gln Lys Gln                 405 410 415 Ser Glu Phe Met Asn Asn Asn Ser Ser Glu Gln Val Leu Tyr Ala Asp             420 425 430 Pro Val Ile Thr Glu Ile Glu Ile Phe Leu Pro Glu Glu His Lys Pro         435 440 445 Thr Asp Tyr Lys Ala Glu Lys Asn Thr Gly Ser Leu Glu Thr Arg Asp     450 455 460 Cys Leu Gln Asn Ser Leu Leu Thr Asn Thr Thr Val Val Tyr Ile Pro 465 470 475 480 Gly Leu Ser Thr Gly Tyr Lys Pro Gln Ile Ser Asn Phe Leu Thr Gly                 485 490 495 Gly Asn His Leu Ser Lys Lys Asp Glu Thr Ser Ser Ser Thr Leu Lys             500 505 510 Pro Leu Ala Asp Ser Ser Asp Leu Gly Gly Asn Ala Arg Phe Lys Lys         515 520 525 Tyr Pro Asn Phe Ala Phe Ser Val Ser Ser Met Asn Ser Leu Ser Asn     530 535 540 Thr Leu Phe Leu Glu Glu Leu Ser Leu Ile Leu Asn Gln Gly Glu Arg 545 550 555 560 Ser Pro Leu Asp Met Gln Asn Ser Val Glu Gly Glu Thr Thr Met Leu                 565 570 575 Leu Glu Asn Ala Ser Pro Asn Glu Thr Ile Pro Glu Gln Thr Leu Leu             580 585 590 Pro Asp Glu Phe Val Ser Cys Leu Gly Ile Met Asn Glu Glu Leu Pro         595 600 605 Ser Ile Asn Ser Tyr Phe Pro Gln Asn Ile Leu Glu Asn His Phe Asn     610 615 620 Thr Ile Ser Leu Leu Glu Lys 625 630 <210> 765 <211> 630 <212> PRT <213> Bos sp. <400> 765 Met Asn Gln Val Thr Ile His Trp Asp Val Val Ile Ala Leu Tyr Ile 1 5 10 15 Phe Phe Ser Trp Cys His Gly Gly Ile Thr Asn Ile Asn Cys Ser Gly             20 25 30 His Ile Trp Val Glu Pro Ala Thr Ile Phe Lys Met Gly Met Asn Ile         35 40 45 Ser Ile Tyr Cys Gln Ala Ala Ile Lys Asn Cys Gln Pro Ser Lys Leu     50 55 60 Tyr Phe Tyr Lys Asn Gly Ile Lys Glu Arg Phe His Ile Thr Arg Ile 65 70 75 80 Asn Lys Thr Thr Ala Arg Leu Trp Tyr Asn Asn Phe Val Glu Pro Gln                 85 90 95 Ala Phe Met Tyr Cys Thr Ala Glu Cys Ser Arg Tyr Phe Pro Glu Thr             100 105 110 Leu Ile Cys Gly Lys Asp Ile Ser Ser Gly Tyr Pro Pro Asp Val Pro         115 120 125 Asp Lys Val Ala Cys Val Ile Tyr Glu Tyr Ser Gly Asn Met Thr Cys     130 135 140 Thr Trp Asn Pro Gly Arg Pro Thr Tyr Ile Asp Thr Lys Tyr Val Val 145 150 155 160 Tyr Val Lys Ser Leu Glu Thr Glu Glu Glu Gln Glu Tyr Leu Thr Ser                 165 170 175 Ser Tyr Ile Asn Ile Ser Thr Asp Ser Leu Gln Lys Gly Lys Lys Tyr             180 185 190 Leu Val Trp Val Gln Ala Ser Asn Val Leu Gly Met Glu Lys Ser Lys         195 200 205 Gln Leu Gln Ile His Leu Asp Asp Ile Val Ile Pro Ser Ala Ser Ile     210 215 220 Ile Ser Arg Ala Glu Asp Ile Asn Thr Thr Val Ser Lys Thr Val Ile 225 230 235 240 His Trp Asp Ser Gln Thr Ser Ile Glu Lys Val Ser Cys Glu Met Arg                 245 250 255 Tyr Lys Ala Thr Thr Asn Gln Thr Trp Asn Val Lys Glu Phe Asp Thr             260 265 270 Asn Phe Thr Tyr Glu Gln Gln Ser Glu Phe Tyr Leu Gln Pro Asn Ala         275 280 285 Met Tyr Val Phe Gln Val Arg Cys Gln Glu Thr Gly Lys Lys Tyr Trp     290 295 300 Gln Pro Trp Ser Ser Pro Phe Phe His Lys Thr Pro Glu Ile Val Pro 305 310 315 320 Gln Val Thr Met Lys Ser Phe Gln His Asp Thr Gln Asn Ser Gly Leu                 325 330 335 Leu Ile Ala Ser Ile Phe Lys Lys His Leu Thr Ser Asp Asn Arg Lys             340 345 350 Gln Asp Ile Gly Leu Leu Leu Gly Met Val Phe Phe Ala Val Met Leu         355 360 365 Ser Val Leu Ser Leu Ile Gly Ile Phe Asn Arg Ser Leu Arg Thr Gly     370 375 380 Ile Lys Arg Arg Ile Leu Leu Leu Ile Pro Lys Trp Leu Tyr Glu Asp 385 390 395 400 Ile Pro Asn Met Glu Asn Ser Lys Val Val Lys Ile Leu Gln Glu Arg                 405 410 415 Asn Glu Phe Met Asn Asn As Ser Ser Glu Gln Val Leu Tyr Val Asp             420 425 430 Pro Val Ile Thr Glu Ile Glu Ile Ile Leu Pro Glu Glu Lys Pro Met         435 440 445 Gly Tyr Lys Lys Glu Asn Asn Thr Gly Cys Leu Glu Arg Lys Glu Ser     450 455 460 Leu Glu Lys Ser Leu Leu Thr Asp Thr Th Val Val Tyr Ile Pro Asp 465 470 475 480 Leu Asn Thr Gly Tyr Lys Pro Gln Ile Ser Ser Phe Leu Pro Gly Gly                 485 490 495 Asn His Leu Ser Asn Asp Asp Glu Thr Ala Ser Ser Ile Leu Glu Pro             500 505 510 Pro Ala Asp Ser Leu Asn Leu Gly Asn Asn Ala Arg Phe Lys Lys Tyr         515 520 525 Pro Asp Phe Ala Phe Ser Val Ser Ser Thr Asn Ser Leu Ser Asn Thr     530 535 540 Leu Phe Leu Glu Glu Leu Asn Leu Ile Leu Asn Gln Gly Glu Cys Ser 545 550 555 560 Pro Pro Asp Met Gln Asn Ser Ile Glu Gly Glu Thr Ala Met Leu Leu                 565 570 575 Glu Asp Leu Leu Asn Glu Thr Ile Pro Glu Gln Thr Leu Leu Pro             580 585 590 Asp Glu Phe Val Ser Cys Leu Gly Ser Met Asn Lys Glu Leu Pro Ser         595 600 605 Ile Asn Ser Tyr Phe Pro Gln Asn Ile Leu Glu Ser His Phe Asn Arg     610 615 620 Ile Ser Leu Leu Glu Lys 625 630 <210> 766 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLeu <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 766 Xaa Gln Thr Trp Gln Cys Phe Xaa Leu Lys Asn Asn 1 5 10 <210> 767 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 767 Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Lys Asn Gly 1 5 10 <210> 768 <400> 768 000 <210> 769 <400> 769 000 <210> 770 <400> 770 000 <210> 771 <400> 771 000 <210> 772 <400> 772 000 <210> 773 <400> 773 000 <210> 774 <400> 774 000 <210> 775 <400> 775 000 <210> 776 <400> 776 000 <210> 777 <400> 777 000 <210> 778 <400> 778 000 <210> 779 <400> 779 000 <210> 780 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-tBu) <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 780 Xaa Gln Thr Trp Gln Cys Phe Trp Lys Glu Asn Gly 1 5 10 <210> 781 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-guanidino) <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 781 Xaa Gln Thr Trp Gln Cys Phe Trp Lys Glu Asn Gly 1 5 10 <210> 782 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 782 Xaa Gln Thr Trp Gln Cys Phe Trp Lys Glu Asn Gly 1 5 10 <210> 783 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-CO2H) <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 783 Xaa Gln Thr Trp Gln Cys Phe Trp Lys Glu Asn Gly 1 5 10 <210> 784 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-phenoxy) <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 784 Xaa Gln Thr Trp Gln Cys Phe Trp Lys Glu Asn Gly 1 5 10 <210> 785 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-CN) <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 785 Xaa Gln Thr Trp Gln Cys Phe Trp Lys Glu Asn Gly 1 5 10 <210> 786 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-Br) <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 786 Xaa Gln Thr Trp Gln Cys Phe Trp Lys Glu Asn Gly 1 5 10 <210> 787 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-NH2) <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 787 Xaa Gln Thr Trp Gln Cys Phe Trp Lys Glu Asn Gly 1 5 10 <210> 788 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe (4-Me) <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 788 Xaa Gln Thr Trp Gln Cys Phe Phe Lys Glu Asn Gly 1 5 10 <210> 789 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 1-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 789 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 790 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeOrn <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 790 Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Lys Asn Gly 1 5 10 <210> 791 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeOrn <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 791 Xaa Gln Thr Trp Gln Cys Xaa Xaa Xaa Lys Asn Gly 1 5 10 <210> 792 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Beep <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 792 Xaa Gln Thr Trp Gln Cys Xaa Xaa Lys Lys Asn Gly 1 5 10 <210> 793 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Cha <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 793 Xaa Gln Thr Trp Gln Cys Xaa Xaa Lys Lys Asn Gly 1 5 10 <210> 794 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 794 Xaa Gln Thr Trp Gln Cys Xaa Xaa Lys Lys Asn Gly 1 5 10 <210> 795 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> 4-Pyridylalanine <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 795 Xaa Gln Thr Trp Gln Cys Ala Xaa Lys Lys Asn Gly 1 5 10 <210> 796 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Beta-homoTyr <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 796 Xaa Gln Thr Trp Gln Cys Tyr Xaa Lys Lys Asn Gly 1 5 10 <210> 797 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-CONH2) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 797 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 798 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 798 Xaa Gln Thr Trp Gln Cys Xaa Xaa Lys Glu Asn Gly 1 5 10 <210> 799 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (4) (4) <223> 2-Nal <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 799 Xaa Gln Thr Xaa Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 800 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (4) (4) <223> 1-Nal <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 800 Xaa Gln Thr Xaa Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 801 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 801 Xaa Gln Thr Tyr Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 802 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 802 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 803 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 803 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly Gly Glu 1 5 10 <210> 804 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 804 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly Ala Glu 1 5 10 <210> 805 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 805 Xaa Ser Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly Gly Glu 1 5 10 <210> 806 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 806 Xaa Gln Thr Trp Gln Cys Phe Trp Lys Lys Asn Gly Gly Glu 1 5 10 <210> 807 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 807 Xaa Gln Thr Trp Gln Cys Tyr Xaa Lys Lys Asn Gly Gly Glu 1 5 10 <210> 808 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 808 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Ser 1 5 10 <210> 809 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 809 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Ala 1 5 10 <210> 810 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 810 Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Lys Asn Gly 1 5 10 <210> 811 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe-4-N3 <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 811 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 812 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 812 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Gln Gly 1 5 10 <210> 813 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <220> <221> MOD_RES &Lt; 222 > (11) <223> Cit <400> 813 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Xaa Gly 1 5 10 <210> 814 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 814 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Val Asn Gly 1 5 10 <210> 815 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Orn <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 815 Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Lys Asn Gly 1 5 10 <210> 816 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Orn <220> <221> MOD_RES &Lt; 222 > (10) <223> Dap <400> 816 Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Xaa Asn Gly 1 5 10 <210> 817 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 817 Xaa Asn Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 818 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (4) (4) <223> Beep <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 818 Xaa Gln Thr Xaa Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 819 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Cha <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 819 Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Lys Asn Gly 1 5 10 <210> 820 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Chg <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 820 Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Lys Asn Gly 1 5 10 <210> 821 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (4) (4) <223> Octgly <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 821 Xaa Gln Thr Gly Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 822 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Octgly <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 822 Xaa Gln Thr Trp Gln Cys Gly Xaa Lys Lys Asn Gly 1 5 10 <210> 823 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> Octgly <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 823 Xaa Gln Thr Trp Gln Cys Phe Gly Lys Lys Asn Gly 1 5 10 <210> 824 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 824 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly Glu 1 5 10 <210> 825 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 825 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Ala Glu 1 5 10 <210> 826 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 826 Xaa Ser Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly Glu 1 5 10 <210> 827 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 827 Xaa Gln Thr Trp Gln Cys Phe Trp Lys Lys Asn Gly Glu 1 5 10 <210> 828 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 828 Xaa Gln Thr Trp Gln Cys Tyr Xaa Lys Lys Asn Gly Glu 1 5 10 <210> 829 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 829 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 830 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys &Lt; 400 > 830 Xaa Gln Thr Gln Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 831 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 831 Xaa Gln Thr His Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 832 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (4) (4) <223> hPhe <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 832 Xaa Gln Thr Phe Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 833 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (4) (4) <223> Glu (Bzl) <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 833 Xaa Gln Thr Glu Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 834 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (4) (4) <223> Beep <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 834 Xaa Gln Thr Xaa Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 835 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (4) (4) <223> Tic <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 835 Xaa Gln Thr Xaa Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 836 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (4) (4) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 836 Xaa Gln Thr Phe Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 837 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (4) (4) <223> Phe (3,4-Cl2) <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 837 Xaa Gln Thr Phe Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 838 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (4) (4) <223> Phe (4-OMe) <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 838 Xaa Gln Thr Phe Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 839 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (4) (4) <223> Orn (Benzyl) <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 839 Xaa Gln Thr Xaa Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 840 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (4) (4) <223> Orn (Benzaldehyde) <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 840 Xaa Gln Thr Xaa Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 841 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe-OCH2CH2NHAc <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 841 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 842 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLeu <400> 842 Xaa Gln Thr Trp Gln Cys Phe Xaa Leu Glu Asn Gly 1 5 10 <210> 843 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (4) (4) <223> Synthesis of 5-hydroxyTrp <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 843 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 844 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (4) (4) <223> 6-chloroTrp <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 844 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 845 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (4) (4) <223> N-MeTrp <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 845 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 846 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (4) (4) <223> 1,2,3,4-Tetrahydro-norharnam <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 846 Xaa Gln Thr Xaa Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 847 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (4) (4) <223> Phe (4-CO2H) <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys] <400> 847 Xaa Gln Thr Phe Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 848 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (4) (4) <223> Phe (4-CONH2) <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 848 Xaa Gln Thr Phe Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 849 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (4) (4) <223> Phe (4-CONH2) <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 849 Xaa Gln Thr Phe Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 850 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (4) (4) <223> Phe (3,4-OMe) <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys &Lt; 400 > 850 Xaa Gln Thr Phe Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 851 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (4) (4) <223> alpha-MePhe <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 851 Xaa Gln Thr Phe Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 852 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (4) (4) <223> Phe (4-CF3) <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 852 Xaa Gln Thr Phe Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 853 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (4) (4) <223> Phe (4-tBu) <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys] <400> 853 Xaa Gln Thr Phe Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 854 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (4) (4) <223> Phe (2,4-Me2) <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 854 Xaa Gln Thr Phe Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 855 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 855 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Asp Asn Gly 1 5 10 <210> 856 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 856 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Gln Asn Gly 1 5 10 <210> 857 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Benzoic acid) <400> 857 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 858 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (succinic acid) <400> 858 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 859 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (glutaric acid) <400> 859 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 860 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (pyroglutamic acid) conjugated through side chain &Lt; 400 > 860 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 861 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (isovaleric acid) <400> 861 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 862 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Palm) <400> 862 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 863 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (PEG1) <400> 863 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 864 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (PEG2) <400> 864 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 865 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Dap (Benzoic acid) <400> 865 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Xaa Asn Gly 1 5 10 <210> 866 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Dap (succinic acid) <400> 866 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Xaa Asn Gly 1 5 10 <210> 867 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Dap (glutaric acid) <400> 867 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Xaa Asn Gly 1 5 10 <210> 868 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Dap (pyroglutamic acid) conjugated through side chain <400> 868 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Xaa Asn Gly 1 5 10 <210> 869 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Dap (IVA) <400> 869 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Xaa Asn Gly 1 5 10 <210> 870 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Dap (PEG1) <400> 870 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Xaa Asn Gly 1 5 10 <210> 871 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Dap (PEG2) <400> 871 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Xaa Asn Gly 1 5 10 <210> 872 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Dap (PEG2-Ac) <400> 872 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Xaa Asn Gly 1 5 10 <210> 873 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 873 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly Xaa Lys 1 5 10 <210> 874 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <220> <221> MOD_RES &Lt; 222 > (13) <223> D-Lys <400> 874 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly Lys 1 5 10 <210> 875 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <400> 875 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly Xaa 1 5 10 <210> 876 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 876 Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Lys Gln Gly 1 5 10 <210> 877 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <400> 877 Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Gln Asn Gly 1 5 10 <210> 878 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <400> 878 Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Glu Asn Gly 1 5 10 <210> 879 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 1-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 879 Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Lys Asn Gly 1 5 10 <210> 880 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) &Lt; 400 > 880 Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Lys Asn Ala 1 5 10 <210> 881 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <400> 881 Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Lys Asn Gly 1 5 10 <210> 882 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe (4-CO2H) <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 882 Xaa Gln Thr Trp Gln Cys Phe Phe Lys Lys Asn Gly 1 5 10 <210> 883 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (2) (2) <223> Dap <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe (4-Phenoxy) <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 883 Xaa Xaa Thr Trp Gln Cys Phe Phe Lys Lys Asn Gly 1 5 10 <210> 884 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (2) (2) <223> Dap <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 884 Xaa Xaa Thr Trp Gln Cys Phe Phe Lys Lys Asn Gly 1 5 10 <210> 885 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (9) <223> Lys (Ac) <400> 885 Xaa Gln Thr Trp Gln Cys Phe Lys Lys Asn Gly 1 5 10 <210> 886 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (2) (2) <223> Dab <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> hPhe <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 886 Xaa Xaa Thr Trp Gln Cys Phe Phe Lys Lys Asn Gly 1 5 10 <210> 887 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (2) (2) <223> Dap <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> Glu (Bzl) <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 887 Xaa Xaa Thr Trp Gln Cys Phe Glu Lys Lys Asn Gly 1 5 10 <210> 888 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-Me-Orn <400> 888 Xaa Gln Thr Trp Gln Cys Phe Trp Xaa Glu Asn Gly 1 5 10 <210> 889 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 889 Xaa Gln Thr Trp Gln Cys Phe Trp Lys Lys Asn Gly 1 5 10 <210> 890 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-Me-Orn <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 890 Xaa Gln Thr Trp Gln Cys Phe Trp Xaa Lys Asn Gly 1 5 10 <210> 891 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-Me-Orn <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 891 Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Lys Asn Gly 1 5 10 <210> 892 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 892 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 893 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Orn <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 893 Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Lys Asn Gly 1 5 10 <210> 894 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (9) <223> Orn <400> 894 Xaa Gln Thr Trp Gln Cys Phe Trp Xaa Glu Asn Gly 1 5 10 <210> 895 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (9) <223> Orn <220> <221> MOD_RES &Lt; 222 > (10) <223> Dap <400> 895 Xaa Gln Thr Trp Gln Cys Phe Trp Xaa Xaa Asn Gly 1 5 10 <210> 896 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (9) <223> Orn <220> <221> MOD_RES &Lt; 222 > (10) <223> Dap (Ac) <400> 896 Xaa Gln Thr Trp Gln Cys Phe Trp Xaa Xaa Asn Gly 1 5 10 <210> 897 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Orn <220> <221> MOD_RES &Lt; 222 > (10) <223> Dap <400> 897 Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Xaa Asn Gly 1 5 10 <210> 898 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Orn <220> <221> MOD_RES &Lt; 222 > (10) <223> Dap (Ac) <400> 898 Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Xaa Asn Gly 1 5 10 <210> 899 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 899 Xaa Gln Thr Trp Gln Cys Phe Trp Leu Glu Asn Gly 1 5 10 <210> 900 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2- (acetyl-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys (Ac) <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 900 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 901 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-Me-Leu <400> 901 Xaa Gln Thr Trp Gln Cys Phe Trp Leu Glu Asn Gly 1 5 10 <210> 902 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 902 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 903 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <220> <221> MOD_RES &Lt; 222 > (11) <223> Dap <400> 903 Xaa Gln Thr Trp Gln Cys Phe Trp Lys Lys Xaa Gly 1 5 10 <210> 904 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 904 Xaa Gln Thr Trp Gln Cys Phe Trp Lys Lys 1 5 10 <210> 905 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (9) <223> Chg <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 905 Xaa Gln Thr Trp Gln Cys Phe Trp Xaa Lys Asn Gly 1 5 10 <210> 906 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2- (acetyl-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys (Ac) <400> 906 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 907 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe (4-CONH2) <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 907 Xaa Gln Thr Trp Gln Cys Phe Phe Lys Lys Asn Gly 1 5 10 <210> 908 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe (3,4-OMe2) <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 908 Xaa Gln Thr Trp Gln Cys Phe Phe Lys Lys Asn Gly 1 5 10 <210> 909 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (2) (2) <223> Dap <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> Tic <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 909 Xaa Xaa Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 910 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (2) (2) <223> Dap <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe (3,4-Cl2) <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 910 Xaa Xaa Thr Trp Gln Cys Phe Phe Lys Lys Asn Gly 1 5 10 <210> 911 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 911 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Gln 1 5 10 <210> 912 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 912 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Asn 1 5 10 <210> 913 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 913 Xaa Thr Thr Trp Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 914 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-Me-Gly (Ethyl) <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 914 Xaa Gln Thr Trp Gln Cys Phe Xaa Gly Lys Asn Gly 1 5 10 <210> 915 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeVal <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 915 Xaa Gln Thr Trp Gln Cys Phe Xaa Val Lys Asn Gly 1 5 10 <210> 916 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeSer <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 916 Xaa Gln Thr Trp Gln Cys Phe Xaa Ser Lys Asn Gly 1 5 10 <210> 917 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (4) (4) <223> Dap <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 917 Xaa Gln Thr Xaa Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 918 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> Dap <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 918 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 919 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 919 Xaa Gln Thr Arg Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 920 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 920 Xaa Gln Thr Trp Gln Cys Phe Arg Lys Lys Asn Gly 1 5 10 <210> 921 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (4) (4) <223> Dap <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> Dap <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 921 Xaa Gln Thr Xaa Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 922 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 922 Xaa Gln Thr Asp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 923 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 923 Xaa Gln Thr Trp Gln Cys Phe Asp Lys Lys Asn Gly 1 5 10 <210> 924 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 924 Xaa Gln Thr Asp Gln Cys Phe Asp Lys Lys Asn Gly 1 5 10 <210> 925 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> D-Lys <220> <221> MOD_RES <222> (2) (2) <223> Abu <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (9) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (10) <223> alpha-MeLeu <400> 925 Lys Xaa Gln Thr Trp Gln Cys Phe Xaa Leu Glu Asn Gly 1 5 10 <210> 926 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 926 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Arg Asn Gly 1 5 10 <210> 927 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Orn <400> 927 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Xaa Asn Gly 1 5 10 <210> 928 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 928 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 929 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> hArg <400> 929 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Arg Asn Gly 1 5 10 <210> 930 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <220> <221> MOD_RES (12). (12) <223> Beta-Ala <400> 930 Xaa Gln Thr Trp Gln Cys Phe Xaa Leu Lys Asn Ala 1 5 10 <210> 931 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Cit <220> <221> MOD_RES &Lt; 222 > (10) <223> Dap <400> 931 Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Xaa Asn Gly 1 5 10 <210> 932 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (2) (2) <223> alpha-Me-Orn <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 932 Xaa Xaa Thr Trp Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 933 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 933 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Asn Asn Gly 1 5 10 <210> 934 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 934 Xaa Ser Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly Gly Glu 1 5 10 <210> 935 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2- (acetyl-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys (Ac) <400> 935 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Gln 1 5 10 <210> 936 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2- (acetyl-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys (Ac) <400> 936 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Asn 1 5 10 <210> 937 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (6) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES <222> (7) (7) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (8) <223> alpha-MeLys <400> 937 Xaa Thr Trp Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 938 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-Me) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 938 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 939 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (3-Me) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 939 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 940 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> hTyr <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 940 Xaa Gln Thr Trp Gln Cys Tyr Xaa Lys Lys Asn Gly 1 5 10 <210> 941 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> alpha-MeTrp <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 941 Xaa Gln Thr Trp Gln Cys Phe Trp Lys Lys Asn Gly 1 5 10 <210> 942 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (2) (2) <223> alpha-MeSer <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 942 Xaa Ser Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 943 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES &Lt; 222 > (3) <223> alpha-MeSer <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 943 Xaa Gln Ser Trp Gln Cys Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 944 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> alpha-MePhe <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 944 Xaa Gln Thr Trp Gln Cys Phe Phe Lys Lys Asn Gly 1 5 10 <210> 945 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <400> 945 Xaa Gln Thr Trp Gln Cys Phe Trp Xaa Glu Asn Gly 1 5 10 <210> 946 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 946 Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Lys Asn Gly 1 5 10 <210> 947 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <220> <221> MOD_RES &Lt; 222 > (11) <223> Dap (Ac) <400> 947 Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Glu Xaa Gly 1 5 10 <210> 948 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <220> <221> MOD_RES &Lt; 222 > (11) <223> Dab (Ac) <400> 948 Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Glu Xaa Gly 1 5 10 <210> 949 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <220> <221> MOD_RES &Lt; 222 > (11) <223> Lys (Ac) <400> 949 Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Glu Lys Gly 1 5 10 <210> 950 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib &Lt; 400 > 950 Xaa Gln Thr Trp Gln Cys Phe Trp Xaa Glu Asn Asn 1 5 10 <210> 951 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLeu <400> 951 Xaa Gln Thr Trp Gln Cys Phe Xaa Leu Glu Asn Asn 1 5 10 <210> 952 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe (3,4-OMe2) <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib &Lt; 400 > 952 Xaa Gln Thr Trp Gln Cys Phe Phe Xaa Glu Asn Gly 1 5 10 <210> 953 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe (3,4-Cl2) <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <400> 953 Xaa Gln Thr Trp Gln Cys Phe Phe Xaa Glu Asn Asn 1 5 10 <210> 954 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLeu <220> <221> MOD_RES &Lt; 222 > (10) <223> Cit <400> 954 Xaa Gln Thr Trp Gln Cys Phe Xaa Leu Xaa Asn Asn 1 5 10 <210> 955 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLeu <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 955 Xaa Gln Thr Trp Gln Cys Phe Xaa Leu Lys Asn Asn 1 5 10 <210> 956 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-Me) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <400> 956 Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Glu Asn Gly 1 5 10 <210> 957 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (3,4-F2) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <400> 957 Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Glu Asn Gly 1 5 10 <210> 958 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (3-CONH2) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <400> 958 Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Glu Asn Gly 1 5 10 <210> 959 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (2,4-Cl2) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <400> 959 Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Glu Asn Gly 1 5 10 <210> 960 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (3-Me) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <400> 960 Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Glu Asn Gly 1 5 10 <210> 961 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-Cl) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <400> 961 Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Glu Asn Gly 1 5 10 <210> 962 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) &Lt; 223 > Phe (4-F) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <400> 962 Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Glu Asn Gly 1 5 10 <210> 963 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (2,4-Cl2,4-OBz) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <400> 963 Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Glu Asn Gly 1 5 10 <210> 964 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLeu <220> <221> MOD_RES &Lt; 222 > (13) <223> D-Lys <400> 964 Xaa Gln Thr Trp Gln Cys Phe Xaa Leu Glu Asn Gly Lys 1 5 10 <210> 965 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (2) (2) <223> Abu <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (9) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (10) <223> alpha-MeLys <400> 965 Glu Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Asn 1 5 10 <210> 966 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> D-Glu <220> <221> MOD_RES <222> (2) (2) <223> Abu <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (9) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (10) <223> alpha-MeLys <400> 966 Glu Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Asn 1 5 10 <210> 967 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (2) (2) <223> Abu <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (9) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (10) <223> alpha-MeLys <400> 967 Arg Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Asn 1 5 10 <210> 968 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> D-Arg <220> <221> MOD_RES <222> (2) (2) <223> Abu <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (9) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (10) <223> alpha-MeLys <400> 968 Arg Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Asn 1 5 10 <210> 969 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (2) (2) <223> Abu <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (9) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (10) <223> alpha-MeLys <400> 969 Phe Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Asn 1 5 10 <210> 970 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> D-Phe <220> <221> MOD_RES <222> (2) (2) <223> Abu <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (9) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (10) <223> alpha-MeLys <400> 970 Phe Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Asn 1 5 10 <210> 971 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> 2-Nal <220> <221> MOD_RES <222> (2) (2) <223> Abu <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (9) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (10) <223> alpha-MeLys <400> 971 Xaa Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Asn 1 5 10 <210> 972 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (2) (2) <223> Abu <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (9) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (10) <223> alpha-MeLys <400> 972 Thr Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Asn 1 5 10 <210> 973 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (2) (2) <223> Abu <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (9) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (10) <223> alpha-MeLys <400> 973 Leu Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Asn 1 5 10 <210> 974 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> D-Gln <220> <221> MOD_RES <222> (2) (2) <223> Abu <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (9) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (10) <223> alpha-MeLys <400> 974 Gln Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Asn 1 5 10 <210> 975 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Acpc <400> 975 Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Glu Asn Asn 1 5 10 <210> 976 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Acbc <400> 976 Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Glu Asn Asn 1 5 10 <210> 977 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Achc <400> 977 Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Glu Asn Asn 1 5 10 <210> 978 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Acvc <400> 978 Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Glu Asn Asn 1 5 10 <210> 979 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Synthesis of 4-amino-4-carboxy-piperidine <400> 979 Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Glu Asn Asn 1 5 10 <210> 980 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> 4-amino-4-carboxy-tetrahydropyran &Lt; 400 > 980 Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Glu Asn Asn 1 5 10 <210> 981 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLeu <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 981 Xaa Gln Thr Trp Gln Cys Phe Xaa Leu Lys Asn Gly 1 5 10 <210> 982 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLeu <400> 982 Xaa Gln Thr Trp Gln Cys Phe Xaa Leu Glu Asn Gly 1 5 10 <210> 983 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLeu <400> 983 Xaa Gln Thr Trp Gln Cys Phe Xaa Leu Gln Asn Gly 1 5 10 <210> 984 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLeu <220> <221> MOD_RES (12). (12) <223> Beta-Ala <400> 984 Xaa Gln Thr Trp Gln Cys Phe Xaa Leu Gln Asn Ala 1 5 10 <210> 985 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLeu <400> 985 Xaa Gln Thr Trp Gln Cys Phe Xaa Leu Gln Asp Gly 1 5 10 <210> 986 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLeu <400> 986 Xaa Gln Thr Trp Gln Cys Phe Xaa Leu Gln Asp Gly 1 5 10 <210> 987 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <220> <221> MOD_RES (12). (12) <223> Beta-Ala <400> 987 Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Gln Asn Ala 1 5 10 <210> 988 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 1,2,3,4-Tetrahydro-norharnam <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <400> 988 Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Gln Asn Gly 1 5 10 <210> 989 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> Synthesis of 5-hydroxyTrp <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <400> 989 Xaa Gln Thr Trp Gln Cys Phe Trp Xaa Gln Asn Gly 1 5 10 <210> 990 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <220> <221> MOD_RES &Lt; 222 > (11) Asn (isobutyl) <400> 990 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asn Gly Asn 1 5 10 <210> 991 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <220> <221> MOD_RES &Lt; 222 > (11) Asp (1,4-diaminoethane) <400> 991 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Lys Asp Gly 1 5 10 <210> 992 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> D-Phe <220> <221> MOD_RES <222> (2) (2) <223> Abu <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (9) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (10) <223> 4-amino-4-carboxy-tetrahydropyran <400> 992 Phe Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Glu Asn Asn 1 5 10 <210> 993 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> D-Arg <220> <221> MOD_RES <222> (2) (2) <223> Abu <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (9) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (10) <223> 4-amino-4-carboxy-tetrahydropyran <400> 993 Arg Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Glu Asn Asn 1 5 10 <210> 994 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> D-Lys <220> <221> MOD_RES <222> (2) (2) <223> Abu <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (9) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (10) <223> alpha-MeLeu <400> 994 Lys Xaa Gln Thr Trp Gln Cys Phe Xaa Leu Glu Asn Gly 1 5 10 <210> 995 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <400> 995 Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Gln Asn Gly 1 5 10 <210> 996 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 996 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 997 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> D-Lys <220> <221> MOD_RES <222> (2) (2) <223> Abu <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (9) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (10) <223> alpha-MeLys <400> 997 Lys Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 998 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OBzl) <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 998 Xaa Gln Thr Trp Gln Cys Phe Trp Lys Glu Asn Gly 1 5 10 <210> 999 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Tyr (Bzl) <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 999 Xaa Gln Thr Trp Gln Cys Tyr Trp Lys Glu Asn Gly 1 5 10 <210> 1000 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> allylGly <220> <221> MOD_RES <222> (6) <223> allylGly <400> 1000 Gly Ala Asp Trp Val Gly Tyr Trp His Thr Phe Gly 1 5 10 <210> 1001 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> allylGly <220> <221> MOD_RES <222> (6) <223> allylGly <400> 1001 Gly Ala Asp Trp Val Gly Tyr Trp His Thr Phe Gly 1 5 10 <210> 1002 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> 2- (3'-butenyl) Gly <220> <221> MOD_RES <222> (6) <223> 2- (4'-pentenyl) Gly <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys &Lt; 400 > 1002 Gly Arg Thr Trp Gln Gly Tyr Trp Arg Lys Phe Gly Xaa Lys 1 5 10 <210> 1003 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> 2- (4'-pentenyl) Gly <220> <221> MOD_RES <222> (6) <223> 2- (3'-butenyl) Gly <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 1003 Gly Arg Thr Trp Gln Gly Tyr Trp Arg Lys Phe Gly Xaa Lys 1 5 10 <210> 1004 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> allylGly <220> <221> MOD_RES <222> (6) <223> 2- (4'-pentenyl) Gly <220> <221> MOD_RES &Lt; 222 &gt; (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 &gt; (14) <223> D-Lys <400> 1004 Gly Arg Thr Trp Gln Gly Tyr Trp Arg Lys Phe Gly Xaa Lys 1 5 10 <210> 1005 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> 2- (4'-pentenyl) Gly <220> <221> MOD_RES <222> (6) <223> allylGly <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 1005 Gly Arg Thr Trp Gln Gly Tyr Trp Arg Lys Phe Gly Xaa Lys 1 5 10 <210> 1006 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> 2- (3'-butenyl) Gly <220> <221> MOD_RES <222> (6) <223> 2- (3'-butenyl) Gly <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 1006 Gly Arg Thr Trp Gln Gly Tyr Trp Arg Lys Phe Gly Xaa Lys 1 5 10 <210> 1007 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> 2- (3'-butenyl) Gly <220> <221> MOD_RES <222> (6) <223> allylGly <220> <221> MOD_RES &Lt; 222 &gt; (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 &gt; (14) <223> D-Lys <400> 1007 Gly Arg Thr Trp Gln Gly Tyr Trp Arg Lys Phe Gly Xaa Lys 1 5 10 <210> 1008 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> allylGly <220> <221> MOD_RES <222> (6) <223> 2- (3'-butenyl) Gly <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 1008 Gly Arg Thr Trp Gln Gly Tyr Trp Arg Lys Phe Gly Xaa Lys 1 5 10 <210> 1009 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Dap <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 1009 Xaa Gln Thr Trp Gln Glu Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 1010 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (6) <223> Dab <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 1010 Glu Gln Thr Trp Gln Xaa Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 1011 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (6) <223> Dap <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 1011 Glu Gln Thr Trp Gln Xaa Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 1012 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Dab <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 1012 Xaa Gln Thr Trp Gln Glu Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 1013 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Dap <220> <221> MOD_RES <222> (6) <223> D-Asp <220> <221> MOD_RES &Lt; 222 &gt; (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 1013 Xaa Gln Thr Trp Gln Asp Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 1014 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Dap <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 &gt; (14) <223> D-Lys <400> 1014 Xaa Gln Thr Trp Gln Asp Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 1015 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (6) <223> Dab <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 1015 Asp Gln Thr Trp Gln Xaa Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 1016 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Dab <220> <221> MOD_RES &Lt; 222 &gt; (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 &gt; (14) <223> D-Lys <400> 1016 Xaa Gln Thr Trp Gln Asp Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 1017 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> D-Dab <220> <221> MOD_RES <222> (6) <223> D-Asp <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 1017 Xaa Gln Thr Trp Gln Asp Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 1018 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> D-Asp <220> <221> MOD_RES <222> (6) <223> D-Dab <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 1018 Asp Gln Thr Trp Gln Xaa Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 1019 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> D-Asp <220> <221> MOD_RES <222> (6) <223> D-Dap <220> <221> MOD_RES &Lt; 222 &gt; (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 &gt; (14) <223> D-Lys <400> 1019 Asp Gln Thr Trp Gln Xaa Tyr Trp Arg Glu Asn Gly Xaa Lys 1 5 10 <210> 1020 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <400> 1020 Xaa Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly 1 5 10 <210> 1021 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (6) <223> Pen <400> 1021 Cys Ala Asp Trp Val Xaa Tyr Trp His Thr Phe Gly 1 5 10 <210> 1022 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> D-Pen <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 1022 Xaa Ala Asp Trp Val Cys Tyr Trp His Thr Phe Gly Xaa Lys 1 5 10 <210> 1023 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (6) <223> D-Pen <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 1023 Cys Ala Asp Trp Val Xaa Tyr Trp His Thr Phe Gly Xaa Lys 1 5 10 <210> 1024 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 1024 Xaa Arg Thr Trp Gln Cys Tyr Trp Arg Lys Phe Gly Xaa Lys 1 5 10 <210> 1025 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 1025 Ala Cys Asp Trp Val Xaa Tyr Trp Arg Lys Phe Gly Xaa Lys 1 5 10 <210> 1026 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (2) (2) <223> Pen <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 1026 Ala Xaa Asp Trp Val Cys Tyr Trp Arg Lys Phe Gly Xaa Lys 1 5 10 <210> 1027 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (2) (2) <223> hCys <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 1027 Ala Cys Asp Trp Val Xaa Tyr Trp Arg Lys Phe Gly Xaa Lys 1 5 10 <210> 1028 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLeu <400> 1028 Cys Gln Thr Trp Gln Xaa Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 1029 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES &Lt; 222 > (9) <223> D-Asn <400> 1029 Cys Gln Thr Trp Gln Xaa Tyr Trp Asn Glu Asn Gly 1 5 10 <210> 1030 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES &Lt; 222 > (9) <223> N-Me-Arg <400> 1030 Xaa Gln Thr Trp Gln Xaa Tyr Trp Arg Glu Asn Gly 1 5 10 <210> 1031 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) [Phe (4-OMe)] (OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeOrn <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 1031 Xaa Gln Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Gly 1 5 10 <210> 1032 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 1032 Xaa Gln Thr Trp Gln Xaa Phe Trp Lys Lys Asn Gly 1 5 10 <210> 1033 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 1033 Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Gly 1 5 10 <210> 1034 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 1034 Xaa Gln Thr Trp Gln Xaa Phe Xaa Lys Lys Asn Asn 1 5 10 <210> 1035 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> D-Phe <220> <221> MOD_RES <222> (2) (2) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Pen <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (9) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (10) <223> Aib <220> <221> MOD_RES &Lt; 222 > (11) <223> Lys (Ac) <400> 1035 Phe Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 1036 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-CONH2) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Acvc <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 1036 Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 1037 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Acvc <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) <400> 1037 Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 1038 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 1038 Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Gly 1 5 10 <210> 1039 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> D-Lys <220> <221> MOD_RES <222> (2) (2) <223> Abu <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (9) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (10) <223> alpha-MeLeu <400> 1039 Lys Xaa Gln Thr Trp Gln Cys Phe Xaa Leu Glu Asn Gly 1 5 10 <210> 1040 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Tyr (Bzl) <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLys <400> 1040 Xaa Gln Thr Trp Gln Cys Tyr Trp Lys Glu Asn Gly 1 5 10 <210> 1041 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> D-Arg <220> <221> MOD_RES <222> (2) (2) <223> Abu <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (9) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (10) <223> alpha-MeLys <400> 1041 Arg Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Asn 1 5 10 <210> 1042 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> D-Gln <220> <221> MOD_RES <222> (2) (2) <223> Abu <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (9) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (10) <223> alpha-MeLys <400> 1042 Gln Xaa Gln Thr Trp Gln Cys Phe Xaa Lys Glu Asn Asn 1 5 10 <210> 1043 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Acpc <400> 1043 Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Glu Asn Asn 1 5 10 <210> 1044 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 1044 Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 1045 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (15) <223> Azt <220> <221> MOD_RES &Lt; 222 > (16) <223> D-Lys <400> 1045 Cys Ala Asp Trp Val Trp Cys Tyr Trp His Thr Phe Gly Ala Xaa Lys 1 5 10 15 <210> 1046 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES &Lt; 222 > (13) (2-aminoethoxy) acetic acid <220> <221> MOD_RES &Lt; 222 > (14) <223> D-Lys <400> 1046 Xaa Arg Thr Trp Gln Cys Tyr Trp Arg Lys Phe Gly Xaa Lys 1 5 10 <210> 1047 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Abu <220> <221> MOD_RES <222> (7) (7) <223> Phe [4- (2-aminoethoxy)] - <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Achc <400> 1047 Xaa Gln Thr Trp Gln Cys Phe Xaa Xaa Glu Asn Asn 1 5 10 <210> 1048 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> D-Phe <220> <221> MOD_RES <222> (2) (2) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Pen <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (9) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (10) <223> 4-amino-4-carboxy-tetrahydropyran <220> <221> MOD_RES &Lt; 222 > (11) <223> Cit <400> 1048 Phe Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Xaa Asn Asn 1 5 10 <210> 1049 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> D-Phe <220> <221> MOD_RES <222> (2) (2) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Pen <220> <221> MOD_RES &Lt; 222 > (8) <223> Phe (4-OMe) <220> <221> MOD_RES &Lt; 222 > (9) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (10) <223> Achc <400> 1049 Phe Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Glu Asn Asn 1 5 10 <210> 1050 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) <223> Pen <220> <221> MOD_RES <222> (6) <223> Pen <220> <221> MOD_RES <222> (7) (7) <223> Phe (CONH2) <220> <221> MOD_RES &Lt; 222 > (8) <223> 2-Nal <220> <221> MOD_RES &Lt; 222 > (9) <223> Aib <220> <221> MOD_RES &Lt; 222 > (10) <223> Lys (Ac) &Lt; 400 > 1050 Xaa Asn Thr Trp Gln Xaa Phe Xaa Xaa Lys Asn Asn 1 5 10 <210> 1051 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 1051 Cys Arg Ser Trp Gln Cys Tyr Trp Asn Lys Phe Gly Ala Asp Asp 1 5 10 15 <210> 1052 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 1052 Cys His Thr Trp Gln Cys Tyr Trp Leu Asn Phe Gly Asp Glu Glu 1 5 10 15 <210> 1053 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 1053 Cys Arg Thr Trp Gln Cys Tyr Trp Leu Asn Phe Gly Asn Glu Gln 1 5 10 15 <210> 1054 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 1054 Cys Arg Thr Trp Gln Cys Tyr Trp Ser Glu Phe Gly Thr Gly Glu 1 5 10 15 <210> 1055 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 1055 Cys Arg Thr Trp Gln Cys Tyr Trp Leu Arg Leu Gly Asp Glu Gly 1 5 10 15 <210> 1056 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 1056 Cys His Thr Trp Gln Cys Tyr Trp Ser Thr Leu Gly Pro Glu Ala 1 5 10 15 <210> 1057 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 1057 Cys Ser Thr Trp Gln Cys Tyr Trp Ser Lys Gln Ser Gly Gly Ser 1 5 10 15 <210> 1058 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 1058 Cys His Thr Trp Gln Cys Tyr Trp Leu Asn Asn Gly Thr Ser Gln 1 5 10 15 <210> 1059 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 1059 Cys His Thr Trp Gln Cys Tyr Trp Arg Ala Asn Asp Gly Arg Asp 1 5 10 15 <210> 1060 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 1060 Ser Gly Cys Arg Thr Trp Gln Cys Tyr Trp His Glu Phe Gly 1 5 10 <210> 1061 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 1061 Asn Lys Cys Arg Thr Trp Gln Cys Tyr Trp His Glu Tyr Gly 1 5 10 <210> 1062 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 1062 Ser Gly Cys Arg Thr Trp Glu Cys Tyr Trp His Glu Tyr Gly 1 5 10 <210> 1063 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 1063 Asp Ala Cys Arg Thr Trp Glu Cys Tyr Trp His Lys Phe Gly 1 5 10 <210> 1064 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 1064 Pro Glu Cys Arg Thr Trp Glu Cys Tyr Trp His Lys Phe Gly 1 5 10 <210> 1065 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 1065 Gln Val Cys Gln Thr Trp Glu Cys Tyr Trp Arg Glu Phe Gly 1 5 10 <210> 1066 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 1066 Asp Arg Cys Val Thr Trp Glu Cys Tyr Trp Arg Glu Phe Gly 1 5 10 <210> 1067 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 1067 Ala Asp Gln Cys Arg Thr Trp Gln Cys Tyr Trp His Glu Phe Gly 1 5 10 15 <210> 1068 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 1068 Lys Glu Asn Cys Arg Thr Trp Glu Cys Tyr Trp Arg Glu Phe Gly 1 5 10 15 <210> 1069 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 1069 Val Gln Glu Cys Ser Thr Trp Gln Cys Tyr Trp Arg Thr Phe Gly 1 5 10 15 <210> 1070 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 1070 Gly Glu Glu Cys Ser Thr Trp Gln Cys Tyr Trp Arg Lys Phe Gly 1 5 10 15 <210> 1071 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 1071 Asp Gly Ser Cys Arg Thr Trp Gln Cys Tyr Trp His Gln Phe Gly 1 5 10 15 <210> 1072 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 1072 Asn Ala Asp Cys His Ser Trp Glu Cys Tyr Trp Arg Glu Phe Gly 1 5 10 15 <210> 1073 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 1073 Glu Arg Asn Cys Ser Thr Trp Glu Cys Tyr Trp Arg Ala Phe Gly 1 5 10 15 <210> 1074 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 1074 Arg Val Gly Cys Ser Thr Trp Glu Cys Tyr Trp Arg Glu Phe Gly 1 5 10 15 <210> 1075 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 1075 Lys Ala Asn Cys Arg Thr Trp Gln Cys Tyr Trp Arg Lys Phe Glu 1 5 10 15 <210> 1076 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 1076 Tyr Glu Asp Cys Arg Thr Trp Gln Cys Tyr Trp Glu Asn Phe Gly 1 5 10 15 <210> 1077 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 1077 Cys Gln Thr Trp Gln Cys Tyr Trp Arg Asn Phe Gly Asp Ser 1 5 10 <210> 1078 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 1078 Cys Gln Thr Trp Gln Cys Tyr Trp Arg Asn Phe Glu Ser Gly 1 5 10 <210> 1079 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 1079 Cys Gln Asp Trp Gln Cys Tyr Trp Arg Glu Phe Gly Pro Gly 1 5 10 <210> 1080 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide &Lt; 400 > 1080 Cys Gln Asp Trp Gln Cys Tyr Trp Arg Ser Phe Gly Pro Gln 1 5 10 <210> 1081 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 1081 Cys Gln Thr Trp Gln Cys Tyr Trp Arg Thr Leu Gly Pro Ser 1 5 10 <210> 1082 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 1082 Cys Arg Thr Trp Gln Cys Tyr Trp Gln Asn Phe Gly 1 5 10 <210> 1083 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 1083 Cys Gly Thr Trp Gln Cys Tyr Trp Arg Thr Phe Gly Pro Ser 1 5 10 <210> 1084 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 1084 Cys Ser Thr Trp Gln Cys Tyr Trp His Lys Phe Gly Asn Glu 1 5 10 <210> 1085 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 1085 Cys Arg Thr Trp Glu Cys Tyr Trp Arg Thr Tyr Gly Pro Ser 1 5 10 <210> 1086 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 1086 Cys Arg Thr Trp Gln Cys Tyr Trp Trp Glu Asn Ser Gln Met 1 5 10 <210> 1087 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 1087 Cys Gln Thr Trp Gln Cys Tyr Trp Arg Glu Phe Gly Gly Gly 1 5 10 <210> 1088 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 1088 Cys Gln Thr Trp Gln Cys Tyr Trp Arg Thr His Gly Asp Arg 1 5 10 <210> 1089 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <400> 1089 Cys Arg Asp Trp Gln Cys Tyr Trp Leu Ser Arg Pro 1 5 10 <210> 1090 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> Lys (Palm) <400> 1090 Cys Gln Thr Trp Gln Cys Tyr Trp Lys Glu Asn Gly 1 5 10 <210> 1091 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> Lys (PEG8) <400> 1091 Cys Gln Thr Trp Gln Cys Tyr Trp Lys Glu Asn Gly 1 5 10 <210> 1092 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 1092 Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Gln Gly 1 5 10 <210> 1093 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (7) (7) <223> D-Tyr <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu <400> 1093 Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 1094 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (7) (7) <223> N-MeTyr <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu   <400> 1094 Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 1095 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (7) (7) <223> Tic-OH <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu   <400> 1095 Cys Gln Thr Trp Gln Cys Xaa Trp Leu Glu Asn Gly 1 5 10 <210> 1096 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu   <400> 1096 Cys Gln Thr Trp Gln Cys Glu Trp Leu Glu Asn Gly 1 5 10 <210> 1097 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu   <400> 1097 Cys Gln Thr Trp Gln Cys Thr Trp Leu Glu Asn Gly 1 5 10 <210> 1098 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (7) (7) <223> Cha <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu   <400> 1098 Cys Gln Thr Trp Gln Cys Xaa Trp Leu Glu Asn Gly 1 5 10 <210> 1099 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> alpha-MeLeu <400> 1099 Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 1100 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> D-Leu <400> 1100 Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 1101 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu   <220> <221> MOD_RES &Lt; 222 > (13) <223> D-Lys <400> 1101 Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly Lys 1 5 10 <210> 1102 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu   <400> 1102 Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gly 1 5 10 <210> 1103 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu   <400> 1103 Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Glu 1 5 10 <210> 1104 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu   <400> 1104 Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Arg 1 5 10 <210> 1105 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu   <400> 1105 Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Phe 1 5 10 <210> 1106 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu   <400> 1106 Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Pro 1 5 10 <210> 1107 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu   <400> 1107 Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Gln 1 5 10 <210> 1108 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu   <400> 1108 Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Asn Leu 1 5 10 <210> 1109 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu   <400> 1109 Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Glu Gly 1 5 10 <210> 1110 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES &Lt; 222 > (9) <223> hLeu   <400> 1110 Cys Gln Thr Trp Gln Cys Tyr Trp Leu Glu Arg Gly 1 5 10 <210> 1111 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) (3) <223> Any amino acid or absent <220> <221> MOD_RES <222> (4) (4) 2-allylglycine, 2- (3'-butenyl) glycine, 2- (4'-pentenyl) glycine,       or 2- (5'-hexenyl) glycine <220> <221> MOD_RES &Lt; 222 &gt; (5) Ala, Arg, Sarc, alpha-MeOrn, alpha-MeSer, Cit, Dap, Dab,       Dap (Ac), Gly, Lys, Asn, N-MeGln, N-MeArg, Orn or Gln <220> <221> MOD_RES <222> (6) Asp, Thr or Asn <220> <221> MOD_RES &Lt; 222 &gt; (8) Val, Gln or Glu <220> <221> MOD_RES &Lt; 222 &gt; (9) 2-allylglycine, 2- (3'-butenyl) glycine, 2- (4'-pentenyl) glycine       or 2- (5'-hexenyl) glycine <220> <221> MOD_RES &Lt; 222 > (11) Trp, 1-Nal, 2-Nal, Phe (3,4-OMe2) 5-Hydroxy-Trp, Phe (3,4-       or Tyr (3-t-Bu) <220> <221> MOD_RES &Lt; 222 > (13) Thr, Sarc, Glu, Phe, Arg, Leu, Lys, Beta-Val, Val, Aib,       Lys (Ac), Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, Orn       or Gln <220> <221> MOD_RES &Lt; 222 > (15) Gly, Ser, Thr, Gln, Ala, Sarc, Beta-Ala, Glu, Arg or Asn <220> <221> MOD_RES &Lt; 222 > (16) <223> Any amino acid or absent <400> 1111 Xaa Xaa Xaa Gly Xaa Xaa Trp Xaa Gly Tyr Xaa His Xaa Phe Xaa Xaa 1 5 10 15 Xaa Xaa Xaa Xaa             20 <210> 1112 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) (3) <223> Any amino acid or absent <220> <221> MOD_RES &Lt; 222 > (5) Glu, Phe, Leu, Thr, Ser, Aib, Sarc, alpha-MeOrn,       alpha-MeSer, Cit, Dap, Dab, Dap (Ac), Gly, Lys, Asn, N-MeGln,       N-MeArg, Orn or Gln <220> <221> MOD_RES <222> (6) Asp, Thr, Asn or Phe <220> <221> MOD_RES &Lt; 222 > (8) Val, Gln, Glu or Lys <220> <221> MOD_RES &Lt; 222 > (11) Trp, 1-Nal, 2-Nal, Phe (3,4-OMe2), 5-Hydroxy-Trp, Phe (3,4-       or Tyr (3-t-Bu) <220> <221> MOD_RES &Lt; 222 > (13) Thr, Sarc, Glu, Phe, Arg, Leu, Lys, Beta-Val, Val, Aib,       Lys (Ac), Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, Orn,       Gln or absent <220> <221> MOD_RES &Lt; 222 > (14) Ac, Gln, Lys (Ac), His, Dap (Ac), Dab (Ac)       Asp or absent <220> <221> MOD_RES &Lt; 222 > (15) Gly, Ser, Thr, Gln, Ala, Sarc, beta-Ala, Glu, Arg, Asn       or absent <220> <221> MOD_RES &Lt; 222 > (16) <223> Any amino acid or absent <400> 1112 Xaa Xaa Xaa Cys Xaa Xaa Trp Xaa Cys Tyr Xaa His Xaa Xaa Xaa Xaa 1 5 10 15 Xaa Xaa Xaa Xaa             20 <210> 1113 <211> 20 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) (3) <223> Any amino acid or absent <220> <221> MOD_RES &Lt; 222 > (5) Ala, Arg, Sarc, alpha-MeOrn, alpha-MeSer, Cit, Dap, Dab,       Dap (Ac), Gly, Lys, Asn, N-MeGln, N-MeArg, Orn or Gln <220> <221> MOD_RES <222> (6) Asp, Thr or Asn <220> <221> MOD_RES &Lt; 222 > (8) Val, Gln or Glu <220> <221> MOD_RES &Lt; 222 > (11) Trp, 1-Nal, 2-Nal, Phe (3,4-OMe2), 5-Hydroxy-Trp, Phe (3,4-       or Tyr (3-t-Bu) <220> <221> MOD_RES &Lt; 222 > (13) Thr, Sarc, Glu, Phe, Arg, Leu, Lys, beta-valine, Val, Aib,       Lys (Ac), Cit, Asp, Dab, Dap, Glu, hArg, Lys, Asn, Orn,       Gln or absent <220> <221> MOD_RES &Lt; 222 > (15) Gly, Ser, Thr, Gln, Ala, Sarc, beta-Ala, Glu, Arg, Asn       or absent <220> <221> MOD_RES &Lt; 222 > (16) <223> Any amino acid or absent <400> 1113 Xaa Xaa Xaa Cys Xaa Xaa Trp Xaa Cys Tyr Xaa His Xaa Phe Xaa Xaa 1 5 10 15 Xaa Xaa Xaa Xaa             20 <210> 1114 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> Description of Artificial Sequence: Synthetic       peptide <220> <221> MOD_RES <222> (1) (3) <223> Any amino acid or absent <220> <221> MOD_RES <222> (5) (6) <223> Any amino acid <220> <221> MOD_RES &Lt; 222 > (8) <223> Any amino acid <220> <221> MOD_RES &Lt; 222 > (10) (3-Me), Phe (3,4-Cl2), Phe (3-Me), Phe       Phe [4- (2-aminoethoxy)], Phe [4- (2- (acetylaminoethoxy)],       Phe (4-Br), Phe (4-CONH2), Phe (4-Cl)       Phe (4-guanidino) Phe (4-Me), Phe (4-NH2)        <220> <221> MOD_RES &Lt; 222 > (10) <223> continued from above; Phe (4-OMe) or Phe (4-OBzl) <220> <221> MOD_RES &Lt; 222 > (11) Trp, 1-Nal, Phe (3,4-OMe2), 5-Hydroxy-Trp, Phe (3,4-Cl2) or       Tyr (3-t-Bu) <220> <221> MOD_RES (12). (12) Arg, Lys, His, hArg, Cit, Orn, 1-Nal, D-Ala, D-Leu, D-Phe,       D-Asn, D-Asp, Agp, Leu, Beta-hLeu, Aib, Beta-       Beta-hArg, hLeu, Dap, 4-amino-4-carboxy-tetrahydropyran, Achc,       Acpc, Acbc, Acvc, Agp, Aib, alpha-DiethylGly, alpha-MeLys, <220> <221> MOD_RES (12). (12) <223> continued from above; alpha-MeLys (Ac), alpha-Me-Leu,       alpha-MeOrn, alpha-MeSer, alpha-MeVal, Cha, Cit, Cpa,       D-Asn, Glu, hArg or Lys <220> <221> MOD_RES &Lt; 222 > (13) Ala, Leu, Val, Dab, Glu, Lys, Beta-hLeu, Beta-hla,       Beta-hVal, Beta-Glu, Lys (Ac), Cit, Asp, Dab, Dap, Glu, hArg,       Lys, Asn, Orn, Lys (Ac) or Gln <220> <221> MOD_RES &Lt; 222 > (14) Ac, Gln, Lys (Ac), His, Dap (Ac), Phe, Tic, Asn, Tyr, Asn,       Dab (Ac) or Asp <220> <221> MOD_RES &Lt; 222 > (16) <223> Any amino acid <220> <221> MOD_RES &Lt; 222 > (17) <223> D-Lys <220> <221> MOD_RES <222> (18). (19) <223> Any amino acid or absent <400> 1114 Xaa Xaa Xaa Cys Xaa Xaa Trp Xaa Cys Xaa Xaa Xaa Xaa Xaa Gly Xaa 1 5 10 15 Lys Xaa Xaa             

Claims (29)

Comprising the amino acid sequence of the following sequence formula (Xa)
Is cyclized through a bond between X &lt; 4 &gt; and X &
23. A peptide inhibitor of an interleukin-23 receptor, or a pharmaceutically acceptable salt or solvate thereof, which inhibits the binding of interleukin-23 (IL-23) to the IL-23 receptor:
(Xa) X1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12-
In this formula,
X1 is any amino acid, or is absent;
X2 is any amino acid, or is absent;
X3 is any amino acid or is absent;
X4 is any amino acid or chemical moiety capable of forming a bond with X9;
X5 is any amino acid;
X6 is any amino acid;
X7 is any amino acid;
X8 is any amino acid;
X9 is any amino acid or chemical moiety capable of forming a bond with X4;
X10 is any amino acid;
X11 is any amino acid;
X12 is any amino acid;
X13 is any amino acid;
X14 is any amino acid;
X15 is any amino acid,
X16 is any amino acid, or is absent;
X17 is any amino acid or is absent;
X18 is any amino acid or is absent;
X19 is any amino acid, or is absent;
X20 is any amino acid or is absent. The method according to claim 1,
Wherein the bond between X4 and X9 is a disulfide bond, a thioether bond, a lactam bond, a triazole ring, a selenoether bond, a diselenide bond, or an olefin bond. The method according to claim 1,
X4 is Cys, X9 is Cys, and the bond is a disulfide bond. The method according to claim 1,
X4 is a Pen, X9 is a Pen, and the bond is a disulfide bond. The method of claim 1,
Wherein the peptide inhibitor comprises an amino acid sequence of any of SEQ ID NOS: 365 to 370, 857 to 1029. &lt; Desc / Clms Page number 36 &gt; The method according to claim 1,
Wherein the peptide inhibitor comprises an amino acid sequence according to any of SEQ ID NOS: Va, Vb, Vc, Vd, Ve, Vf, Vg and Vh. Inhibitor. The method according to claim 1,
Wherein the peptide inhibitor comprises any of the following amino acid sequences:
[Palm] - [Iso Glu] - [PEG4] - [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys Ac)] - &lt; / RTI &_gt;NNNH2;
Ac- [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys (PEG4- NH ₂ ;
Ac- [Pen] -QTWQ- [Pen] -Phe (4-CONH 2) - [2-Nal] - [α-MeLys (Ac)] - [Lys (Ac)] - NN-NH 2;
[Octyl] - [iso Glu] - [PEG4] - [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys (Ac)] - NN-NH 2;
(Ac)] - [2-Nal] - [Aib] - [PEG4] - [Pen] -NTWQ- [Pen] - [Phe 4- (2-aminoethoxy) NN-NH _2;
[Palm] - [PEG4] - [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] -NH ₂ ;
Ac- [Pen] -NTWQ- [Pen] - [Phe [4- ( 2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys (PEG4- octa-carbonyl)] - NN-NH ₂ ;
Ac- [Pen] -NTWQ- [Pen] - [Phe [4- ( 2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys (PEG4-Palm)] - NN-NH 2;
Ac- [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy) - (PEG4- Palm)] - [2-Nal] - [Aib] NH ₂ ;
Ac- [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy) - (PEG4-lauryl)] - [2-Nal] - [Aib] NN-NH _2;
Ac- [Pen] -QTWQ- [Pen] -Phe (4-CONH 2) - [2-Nal] - [α-MeLys (PEG4-Palm) - [Lys (Ac)] - NN-NH 2;
Ac- [Pen] -QTWQ- [Pen] -Phe (4-CONH 2) - [2-Nal] - [α-MeLys (PEG4- lauryl)] - [Lys (Ac) ] - NN-NH 2;
Ac- [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy) - (PEG4-iso Glu- Palm)] - [2-Nal] - [Aib] ] -NN-NH _2;
Ac- [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy) - (PEG4-iso Glu-lauryl)] - [2-Nal] - [Aib] )] - NN-NH _2;
Ac- [Pen] -QTWQ- [Pen] -Phe (4-CONH 2) - [2-Nal] - [α-MeLys (PEG4- iso-Glu-Palm)] - [Lys (Ac)] - NN-NH ₂ ;
Ac- [Pen] -QTWQ- [Pen] -Phe (4-CONH 2) - [2-Nal] - [α-MeLys (PEG4- isopropyl Glu- lauryl)] - [Lys (Ac) ] - NN- NH ₂ ;
Ac- [Pen] -QTWQ- [Pen] -Phe (4-CONH 2) - [2-Nal] - [α-MeLys (IVA)] - [Lys (Ac)] - NN-NH 2;
Ac- [Pen] -QTWQ- [Pen] -Phe (4-CONH 2) - [2-Nal] - [α-MeLys ( Biotin)] - [Lys (Ac) ] - NN-NH 2;
Ac- [Pen] -QTWQ- [Pen] -Phe (4-CONH 2) - [2-Nal] - [α-MeLys ( octa-carbonyl)] - [Lys (Ac) ] - NN-NH 2;
Ac- [Pen] - [Lys (IVA)] - TWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] NN-NH _2;
Lys (Ac)] - [Lys (IVA)] - [2-Nal] - [Aib] N-NH _2;
Ac- [Pen] - [Lys (Biotin)] - TWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] NN-NH _2;
Ac- [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys (Ac)] - [Lys N-NH _2;
Ac- [Pen] - [Lys (octanyl)] - TWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] -NN-NH _2;
Ac- [Pen] -NTWQ- [Pen] - [Phe 4- (2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys (Ac)] - [Lys (octanyl) -N-NH _2;
Ac- [Pen] - [Lys (Palm)] - TWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] -NN-NH _2;
Ac- [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys -NH ₂ ;
Ac- [Pen] - [Lys (PEG8)] - TWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] NN-NH _2;
Ac- [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys (Ac)] - [Lys (PEG8) N-NH _2;
[Ac] - [Lys (Ac)] - NN [Ac- [Pen] -K (Pegll-Palm) TWQ- [Pen] - [Phe 4- -NH ₂ ;
Ac- [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys (Ac)] - [Lys )] - N-NH _2;
Ac- [Pen] - [Cit] -TW- [Cit] - [Pen] - [Phe 4- (2-aminoethoxy)] - [2- ] -NN-NH _2;
Ac- [Pen] - [Lys (Ac)] - TW- [Cit] - [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] _{Ac)] - NN-NH 2} ;
[Ac-Phe] -NT- [Phe (3,4-OCH3) 2] -Q- [Pen] - [Phe [4- (2-aminoethoxy)] - [2- [Lys (Ac)] - NN -NH 2;
[2-Nal] - [Aib] - [Phe] [4- (2-aminoethoxy)] - [2- [Lys (Ac)] - NN -NH 2;
Ac- [Pen] -NT- [Phe (3-CH3)] - Q- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] _{Ac)] - NN-NH 2} ;
[Ac- [Pen] -NT- [Phe (4-CH3)] - Q- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] _{Ac)] - NN-NH 2} ;
Ac [(D) Arg] - [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [βAla] -NH _2;
Ac - [(D) Tyr] - [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] N- [βAla] -NH _2;
Ac- [Pen] -NTWQ- [Pen] - [Phe [4- ( 2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys (Ac)] - QN-NH 2;
Ac- [Pys] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys N-NH _2;
(Ac) - [Lys (Ac)] - [Lys (Ac)] - [Phen] -NTWQ- [Pen] - [Phe 4- (2-aminoethoxy)] - [2- ] -NH _2;
Ac- [Pen] -NTWQ- [Pen] - [Phe [4- ( 2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys (Ac)] - QQ-NH 2;
Ac- [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys ₂ ;
Ac- [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys ₂ ;
Ac- [Pen] -NTWQ- [Pen] - [Phe [4- ( 2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys (Ac)] - [Cit] -NNH 2;
Ac- [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys ₂ ;
Ac- [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys Ac)] - NH _2;
Ac- [Pys] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys [Cit] -NH _2;
Ac- [Pen] -NTWQ- [Pen] - [Phe [4- ( 2-aminoethoxy)] - [2-Nal] - [Aib] -QN- [βAla] -NH 2;
Ac- [Pen] -NTWQ- [Pen] - [Phe [4- ( 2-aminoethoxy)] - [2-Nal] - [Aib] -E- [Cit] -Q-NH 2;
Ac- [Pen] -NTWQ- [Pen] - [Phe [4- ( 2-aminoethoxy)] - [2-Nal] - [Aib] - [Cit] -N- [Cit] -NH 2;
Ac- [Pen] -NTWQ- [Pen] - [Phe [4- ( 2-aminoethoxy)] - [2-Nal] - [Aib] - [Cit] -Q- [Cit] -NH 2;
(Ac) - NN-NH- [Phe] [4- (2-aminoethoxy)] - [2-Nal] - [Aib] ₂ ;
Ac- [Pen] -NTWQ- [Pen] - [Phe [4- ( 2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys (Ac)] - NN-NH 2;
Ac- [Pen] -NTWQ- [Pen] - [Phe [4- ( 2-aminoethoxy)] - [2-Nal] - [Aib] -QNN-NH 2;
Ac [Pen] -NTWQ- [Pen] - [Phe [4- ( 2-aminoethoxy)] - [2-Nal] - [Aib] -ENQ-NH 2;
Ac- [Pen] -GPWQ- [Pen] - [Phe [4- ( 2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys (Ac)] - NN-NH 2;
Ac- [Pen] -PGWQ- [Pen] - [Phe [4- ( 2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys (Ac)] - NN-NH 2;
Ac- [Pen] -NTWN- [Pen] - [Phe [4- ( 2- amino)] - [-2 Nal] - [Aib] - [Lys (Ac)] - NN-NH _2;
Ac- [Pen] -NSWQ- [Pen] - [Phe [4- ( 2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys (Ac)] - NN-NH 2;
(Ac) -NN [Aib] -WQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] -NH ₂ ;
Ac- [Pen] -NTW- [Aib] - [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys ] -NH _2;
[Ac] - [Lys (Ac)] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] NN-NH _2;
Ac- [Pen] - [Lys (Ac)] - TWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2- NNNH ₂ ;
Ac- [Pen] -QVWQ- [Pen] - [Phe [4- ( 2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys (Ac)] - NN-NH 2;
Ac- [Pen] -NT- [2-Nal] -Q- [Pen] - [Phe [4- (2-aminoethoxy)] - [2- -NN-NH _2;
Ac- [Pen] -NT- [l-Nal] -Q- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] -NN-NH _2;
Ac- [Pen] -NTWQ- [Pen] - [Phe [4- ( 2-aminoethoxy)] - [2-Nal] - [α-MeLeu] - [Lys (Ac)] - NN-NH 2;
Ac- [Pen] -NTWQ- [Pen] - [Phe [4- ( 2-aminoethoxy)] - [2-Nal] - [α-MeLys] - [Lys (Ac)] - NN-NH 2;
Ac- [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] )] - NN-NH _2;
Ac- [Pen] -NTWQ- [Pen] - [Phe 4- (2-aminoethoxy)] - [2-Nal] - [α- MeLeu] - [Lys -NH ₂ ;
Ac- [Pen] -NTWQ- [Pen] - [Phe 4- (2-aminoethoxy)] - [2-Nal] - [ -NH ₂ ;
Ac- [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] )] - N- [βAla] -NH 2;
Ac- [Pen] -NTWQ- [Pen] -Phe [4- ( 2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys (Ac) -LN-NH 2;
Ac- [Pen] -NTWQ- [Pen] -Phe [4- ( 2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys (Ac) -GN-NH 2;
Ac- [Pen] -NTWQ- [Pen] -Phe [4- ( 2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys (Ac)] - SN-NH 2;
Ac- [Pen] -NTWQ- [Pen] -Phe [4- ( 2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys (Ac)] - [Aib] -N-NH 2 ;
Ac- [Pen] -NTWQ- [Pen] -Phe [4- ( 2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys (Ac)] - FN-NH 2;
(Ac) - NN-NH- [Pen] -NTW- [Cit] - [Pen] - [Phe 4- (2-aminoethoxy)] - [2-Nal] - [Aib] ₂ ;
Ac- [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys -NH ₂ ;
Ac- [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys (Ac)] - [nLeu] -NH ₂ ;
Ac- [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys ₂ ;
Ac- [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys ₂ ;
Ac- [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys NH ₂ ;
Ac- [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys NH ₂ ;
Ac- [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys ₂ ;
Ac- [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys -NH ₂ ;
Ac- [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys (Ac)] - [N-MeAla] [βAla] -NH _2;
Ac- [Pen] -NTWQ- [Pen] - [Phe [4- (2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys βAla] -NH _2;
Ac- [Pen] -NTWQ- [Pen] - [Phe [4- ( 2-aminoethoxy)] - [2-Nal] - [Aib] - [Lys (Ac) F- [βAla] -NH 2;
- [2-Nal] - [4-amino-4-carboxy-tetrahydrobenzo [ pyran] - [Lys (Ac)] NNNH 2;
[2-Nal] - [4-amino-4-carboxy-tetrahydropyran] -ENN [Phe] -NH ₂ ;
(Ac) -cyclo [[Abu] -QTWQC] - [Phe [4- (2-aminoethoxy)] - [2-Nal] ] -NN-NH _2;
- [2-Nal] - [4-amino-4-carboxy-tetrahydropyran-4-yl] ] - [Lys (Ac)] - NN-NH 2;
- [2-Nal] - [4-amino-4-carboxy-tetrahydropyran-4-yl] ] - [Lys (Ac)] - NN-NH 2;
Ac-E - [(D) Arg] -cyclo [[Abu] -QTWQC] - [Phe [4- (2-aminoethoxy)] - [2- tetrahydropyran] -ENN-NH _2;
- [2-Nal] - [4-amino-isoquinolin-2-yl] - [ 4-carboxy-tetrahydropyran] -ENN-NH _2;
Ac-R - [(D) Arg] -cyclo [[Abu] -QTWQC] - [Phe [4- (2-aminoethoxy)] - [2- tetrahydropyran] -ENN-NH _2;
Ethoxy- Eno)] - [2-Nal] - [4- amino-4-carboxy-tetrahydropyran] -ENN-NH _2;
Ac-F - [(D) Arg] -cyclo [[Abu] -QTWQC] - [Phe [4- (2-aminoethoxy)] - [2- tetrahydropyran] -ENN-NH _2;
[(2-Nal) - [4-Amino-2-amino-isoquinoline- 4-carboxy-tetrahydropyran] -ENN-NH _2;
[2-Nal] - [4-Amino-4 (2-amino) ethoxy] - [2-Nal] - [(D) Arg] -cyclo [[Abu] -QTWQC] - carboxy-tetrahydropyran] -ENN-NH _2;
Ac-T - [(D) Arg] -cyclo [[Abu] -QTWQC] - [Phe [4- (2-aminoethoxy)] - [2- tetrahydropyran] -ENN-NH _2;
Ac-L - [(D) Arg] -cyclo [[Abu] -QTWQC] - [Phe [4- (2-aminoethoxy)] - [2- tetrahydropyran] -ENN-NH _2;
- [2-Nal] - [4-amino-isoxazol-4-yl] - [ 4-carboxy-tetrahydropyran] -ENN-NH _2;
- [2-Nal] - [4-amino-isoquinolin-2-yl] - [ 4-carboxy-tetrahydropyran] -ENN-NH _2;
- [2-Nal] - [4-amino-4-carboxy-tetrahydropyran] - [Phe [4- (2-aminoethoxy) - (PEG4-Alexa488)] - -ENN-NH _2;
- [2-Nal] - [4-amino-4-carboxy-tetrahydropyran] -acetic acid [Alexa488] - [PEG4] -cyclo [[Abu] -QTWQC] -ENN-NH _2;
[Phe] [4- (2-aminoethoxy)] - [2-Nal] - [4-amino-4- carboxy-tetrahydropyran- -ENN-NH _2;
[Phe [4- (2-aminoethoxy)] - [2-Nal] - [4-amino 4-carboxy-tetrahydropyran] - [Lys (Ac)] - NN-NH 2;
- [Phe [4- (2-aminoethoxy)] - [2-Nal] - [4-amino-4- - carboxy-tetrahydropyran] - [Lys (Ac)] - NN-NH 2; And
- [Phe [4- (2-aminoethoxy)] - [2-Nal] - [4-amino-4- - carboxy-tetrahydropyran] - [Lys (Ac)] - NN-NH 2,
Wherein the peptide inhibitor is cyclized through a disulfide bond between two Pen residues or a thioether bond between the Abu and Cys residues and inhibits the binding of interleukin-23 (IL-23) to the IL-23 receptor. Peptide inhibitors. 8. The method according to any one of claims 1 to 7,
Wherein the peptide inhibitor further comprises one or more half-life extension moieties and / or one or more linker moieties conjugated to the peptide inhibitor. 9. The method of claim 8,
Wherein the half-life extension moiety is conjugated to the peptide inhibitor via one or more linker moieties. 10. The method according to any one of claims 1 to 9,
A peptide inhibitor, or a pharmaceutically acceptable salt or solvate thereof, wherein the peptide inhibitor comprises a structure of formula (I): &lt; EMI ID =
R ¹ -XR ² (I)
In this formula,
R ¹ comprises a bond, hydrogen, C ¹ -C 6 alkyl, C 6 -C 12 aryl, C 6 -C 12 aryl, C 1 -C 6 alkyl, C 1 -C 20 alkanoyl, and the PEGylated version of any of the foregoing, ; X is an amino acid sequence;
R ² is OH or NH ₂ . Wherein the peptide monomer subunit comprises two peptide monomer subunits linked via one or more linker moieties, each peptide monomer subunit having a sequence or structure according to any one of claims 1 to 10. Peptide dimer inhibitors. 12. The method of claim 11,
Wherein one or both of the peptide monomer subunits is cyclized via an intramolecular bond between X4 and X9. 13. The method of claim 12,
Wherein one or both of the intramolecular bonds are a disulfide bond, a thioether bond, a lactam bond, a selenoether, a diselenide, or an olefin bond. 14. The method according to any one of claims 11 to 13,
Wherein the linker moiety is a diethylene glycol linker, an iminodiacetic acid (IDA) linker, a beta -Ala-iminodiacetic acid (beta -Ala-IDA) linker, or a PEG linker. 15. The method according to any one of claims 11 to 14,
Wherein the N-terminus of each peptide monomer subunit is linked by a linker moiety, or the C-terminus of each peptide monomer subunit is linked by a linker moiety. 16. The method according to any one of claims 1 to 15,
Wherein the peptide inhibitor or peptide dimer further comprises a conjugated chemical substituent. 17. The method of claim 16,
Wherein the conjugated chemical substituent is a lipophilic substituent or polymer moiety. 17. The method of claim 16,
Wherein the conjugated chemical substituent is selected from the group consisting of Ac, Palm, gamma Glu-Palm, iso Glu-Palm, PEG2-Ac, PEG4-iso Glu-Palm, (PEG) ₅ -Palm, succinic acid, glutaric acid, pyroglutaric acid, IVA, octanoic acid, 1,4-diaminobutane, isobutyl or biotin. 17. The method of claim 16,
Wherein the conjugated chemical substituent is a polyethylene glycol having a molecular mass of 400 Da to 40,000 Da. 17. A polynucleotide comprising a sequence encoding one or both of the peptide inhibitor of any one of claims 1 to 10 or the peptide monomer subunit of the peptide dimer inhibitor of any one of claims 11 to 15. 20. A vector comprising the polynucleotide of claim 20. 20. A pharmaceutical composition comprising a peptide inhibitor or a peptide dimer inhibitor of any one of claims 1 to 19, and a pharmaceutically acceptable carrier, excipient, or diluent. 23. The method of claim 22,
Lt; RTI ID = 0.0 &gt; enteric coating. &Lt; / RTI &gt; 24. The method of claim 23,
Wherein the enteric coating protects and releases the pharmaceutical composition in the lower gastrointestinal tract of the subject. Comprising administering to a subject an effective amount of a peptide inhibitor or a peptide dimer inhibitor of any one of claims 1 to 19 or a pharmaceutical composition of any one of claims 22 to 24. A method for treating inflammatory bowel disease (IBD), ulcerative colitis, Crohn's disease, celiac disease ( non-tropical Sprue), serum response chapters related arthropathy of voice disorders, fine colitis, collagen colitis, eosinophilic gastroenteritis, colitis associated with chemotherapy or radiation therapy, leukocyte adhesion deficiency-1, chronic granulomatosis, glycogen accumulation disease type 1b, Colitis associated with congenital immunity, such as in Hermansky-Pudlak syndrome, Chediak-Higashi syndrome, and Wiskott-Aldrich syndrome, colonic resection And methods of treating gastrointestinal cancer, pancreatitis, insulin-dependent diabetes mellitus, mastitis, cholecystitis, cholangitis, bile duct peritonitis, chronic bronchitis, chronic sinusitis, asthma, psoriasis, psoriatic arthritis, or graft versus host disease caused by ileostomy . 26. The method of claim 25,
The pharmaceutical composition may be administered to a subject in a form suitable for oral, parenteral, intravenous, intraperitoneal, intraperitoneal, subcutaneous, intramuscular, intrathecal, inhalation, vaginal, spray, sublingual, buccal, parenteral, rectal, , Vaginal, or topical routes of administration. 26. The method of claim 25,
Providing a pharmaceutical composition orally to a subject and treating inflammatory bowel disease (IBD), ulcerative colitis, Crohn's disease. 26. The method of claim 25,
Wherein the pharmaceutical composition is provided to a subject orally, topically, parenterally, intravenously, subcutaneously, intraperitoneally, or intravenously, and psoriasis is treated. 29. The method according to any one of claims 25 to 28,
Wherein the peptide inhibitor or peptide dimer inhibitor inhibits the binding of interleukin-23 (IL-23) to the interleukin-23 receptor (IL-23R).

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